bluuebunny/crossref_metadata_2025 huggingface dataset:
MON-LB64 Primary Hyperparathyroidism With Severe Hypercalcemia During Pregnancy: A Challenging Diagnosis and Management
Authors: George Gemy M , Slotcavage Rachel L , Ambrogini Elena
Published: May 2020

Background:Primary Hyperparathyroidism (PHPT) is rare in pregnancy and the physiological adaptations in mineral and skeletal homeostasis that occur during gestation need to be taken into consideration for the diagnosis and management. Clinical case:A 30-year-old primgravid woman with history of kidney stones presented at our institution during the 13th week of twin gestation with severe nausea and vomiting. She had previously been hospitalized at 9 weeks for hypercalcemia and acute kidney injury, and treated with steroids for presumed granulomatous disease without improvement. She was on prenatal vitamins and family history was significant for kidney stones, but not hypercalcemia. At admission, calcium was 14.4 mg/dl, ionized calcium 1.89 mmol/L (1.16-1.32), PTH 15.2 pg/ml (12-88), albumin 3.4 g/dl, phosphorus 2.1 mg/dl, and creatinine 1.8 mg/dl. PTHrP was <2 pmol/L (<4.2) and 1, 25-dihydroxyvitamin D was 191 pg/mL (2nd trimester range 72-160 pg/ml). She was treated with IV hydration, but her calcium remained elevated and severe hypercalcemia recurred after stopping hydration. She underwent neck exploration and right upper parathyroidectomy in the second trimester. The other parathyroid glands were noted to be normal. Intraoperative PTH dropped from 25.2 pg/mL to 4.4 pg/mL. Final pathology showed a hypercellular parathyroid. Her calcium dropped to normal levels in the early postoperative period. Calcitonin was initiated by another provider two weeks postoperatively for persistent mild hypercalcemia. Her calcium levels remained at the upper limit of normal during her 2nd and 3rd trimesters. PTH remained suppressed at 3.2 pg/ml. She had a C-section at 34 weeks for premature rupture of membranes. Her twins did not develop hypocalcemia or hypoparathyroidism. The most recent postpartum calcium was 9.2 mg/dl with PTH 3.3 pg/ml.Conclusions:Our case highlights the challenge in the diagnosis and management of PHPT in pregnancy. During pregnancy, PHPT is diagnosed by elevated ionized or albumin corrected calcium and non-suppressed PTH level. It is important to note that 1,25-dihydroxyvitamin D levels physiologically increase in the second and third trimester. Since both PHPT and pregnancy cause intestinal calcium absorption and bone resorption, PHPT during pregnancy has increased risk of severe hypercalcemia, pancreatitis and renal stones. During the third trimester the transfer of calcium through the placenta and the uptake of calcium by the fetal skeleton can protect against severe hypercalcemia. However, hypercalcemic crisis can occur because of the peak release of PTHrP by the placenta and breasts, or after delivery due to loss of calcium transfer to the placenta. Parathyroidectomy is preferably performed in the second trimester to reduce fetal and maternal complications. After delivery neonatal hypocalcemia can have a delayed onset, a prolonged course and could be permanent.
MON-LB301 Application of Lean Six-Sigma DMAIC Tool for Improvement and Sustainability of Diabetes Management in Outpatient Clinics
Authors: Bernuy Mario C Rivera , Usha Kollipara , Burks Jessica , Fish Jason , Ali Sadia
Published: May 2020

DMAIC: Define, Measure, Analyze, Improve, Control. LSL: Lower specified limit. USL: Upper specified limit.

Lean Six Sigma DMAIC is quality improvement methodology used for strategic business management. Frequent applications of this methodology in healthcare include improvement of patient satisfaction, reduction of emergency department waiting times, prescription error reduction and monetary recovery by reducing waste.

Patients with a HgbA1c testing frequency of >6 months have poorer glycemic control. The American Diabetes Association recommends HgbA1c test quarterly in patients whose therapy has changed or who are not meeting glycemic goals and at least two times a year in patients who are meeting treatment goals.

We hypothesized that the Lean Six-Sigma DMAIC tools can be used in the outpatient clinic setting to improve frequency of HgbA1c testing in patients with diabetes mellitus.

At baseline, 19% of our patients with diabetes mellitus had HgbA1c tested infrequently, defined as more than 6 months. This high percentage is a concern as it could lead to poor diabetes control. The aim was to increase percentage of patients having an HgbA1c tested between 3 to 6 months before an appointment in our clinic, to a goal of 90%. Target population included all patients with diabetes mellitus seen in outpatient endocrinology clinic.

A baseline analysis of existing processes was done through brainstorming with the clinic staff using a fish bone diagram. Lack of follow up and HgbA1c testing orders were some of the modifiable factors identified. The new processes implemented include nurse driven standing medical orders for HgbA1c testing and pre-visit planning. Control phase included regular audits to sustain the improvements.

The percentage of patients with a HgbA1c testing within 3-6 months of appointment improved from a baseline of 76.7% (LSL:70%, USL:94%) to 92.2% (LSL:88%, USL:93.7%). The improvement was noticeable within 1 month of new process implementation and continues to sustain. The mean had an absolute improvement of 15.5%. The variation from the mean decreased from 25% at baseline to 6% at the end of the control phase. The reduction in variation made our future results more predictable.

The use of Lean Six-Sigma DMAIC quality improvement tools are an effective method to improve quality of care in the outpatient setting. These strategies can be replicated for other clinical quality outcomes.
MON-LB104 Update on Anti-Obesity Medical Devices
Authors: Heshmati Hassan M
Published: May 2020

Background: Obesity is excess body weight for a given height. It is a worldwide pandemic associated with increased morbidity/mortality and high cost for the society. The prevalence of obesity has doubled in more than 70 countries since 1980. The prevalence of obesity in the United States of America (USA) is near 40% and its annual medical cost is around $200 billion. Management of obesity requires multidisciplinary approaches. Available options for weight reduction include diet, food supplement, exercise, behavior change, drug, medical device, gut microbiome manipulation, and surgery. In the USA, only 2% of subjects with obesity receive anti-obesity drugs. Properties and Mechanisms of Action: Anti-obesity medical devices represent a heterogenous family in terms of regulation, presentation, usage/administration, mechanism of action, effectiveness, safety, availability, and cost. Unlike anti-obesity drugs that act chemically through specific receptors, anti-obesity medical devices act rather mechanically. They do not have systemic absorption, specific metabolism, or receptors, and, therefore, have no side effects related to the impact on different organs through the bloodstream. Anti-obesity medical devices can cause weight loss through different mechanisms. They can cause a decrease in food intake at the level of oral cavity (by limiting the bite size) or stomach (by reducing the available stomach volume), or can cause a decrease in the amount of available/absorbed nutrient at the level of stomach (by removing part of the gastric contents) or intestine (by bypassing part of the intestine). In the USA, the Center for Devices and Radiological Health (CDRH) of the Food and Drug Administration is approving/clearing the anti-obesity medical devices. Based on the expected weight loss, CDRH categorizes medical devices as weight-loss devices (“more” weight loss) or weight-management devices (“less” weight loss). The weight-loss devices include gastric band devices, gastric space-occupying devices, and gastric emptying devices. The weight-management devices include oral removable palatal space-occupying devices and ingested transient gastric space-occupying devices. Anti-obesity medical devices should be used in conjunction with healthy lifestyle including diet and exercise. The degree of weight loss, the side effects, and the cost of anti-obesity medical devices vary considerably by the type of medical device. Conclusion: Anti-obesity medical devices are an option for subjects who have not responded to more conservative treatments (lifestyle, drugs) but who want an alternative to more aggressive interventions (bariatric surgery). Given the large market size of obesity treatment and the current level of undertreatment with anti-obesity drugs, anti-obesity medical devices can play a major role in the management of obesity.
SUN-LB76 Euthyroid Ophthalmopathy in Coexistence With Differential Thyroid Carcinoma
Authors: Garate Dioni , Villarreal Adriana , Alfaro Gisella , Salsavilca Elizabeth , Chiu Erika
Published: May 2020

Introduction: Thyroid ophthalmopathy (TAO) is a rare autoimmune disorder in euthyroid patients; less frequent in those with negative autoantibodies and thyroid cancer. TSH-R stimulating antibodies bind to said receptor in orbital fibroblasts, producing the secretion of cytokines, hyaluronic acid and adipogenesis that contribute to TAO1. Clinical case: 54-year-old woman has had orbital alterations compatible with TAO for four years, CAS score 2/7-Eugogo Mild, studies of thyroid function and TSI/AbTPO/AbTg antibodies in normal ranges; therefore, she received oral corticotherapy and subtenonial corticosteroid injections. She was subsequently evaluated in Endocrinology, where goiter was found. Thyroid ultrasound showed hypoechogenic left thyroid nodule (14 mm), FNA: Bethesda VI and Pathological anatomy: Papillary thyroid carcinoma. She received ablative therapy with I-131 (30 mCi). Currently with excellent response. During follow-up, ophthalmologic evaluation showed: CAS score 0/10 and VISA score 0/10. Presents palpebral retraction, corneal erosions and PIO elevation. In Tomography: increase in volume of the lacrimal glands and extraocular muscles predominantly in the upper and medial rectum, as well as a thickening of the upper eyelid lift muscle, with greater involvement in the left orbit. These findings are compatible with inactive TAO with an expansive “white eye” phenotype, generally with a lower risk of compressive neuropathy.Discussion: In addition to normal thyroid function and mild TAO, the patient has the characteristic of presenting negative antibodies. Associated with TSH-R, factors such as IGF-1 can be found in the pathogenesis of TAO, which can generate a similar effect1. Likewise, IGF-1 stimulates cell proliferation, and is related to neoplasms such as thyroid carcinoma2. Conclusions Differentiated thyroid carcinoma should be ruled out in all patients with TAO, whether euthyroid or not. Studies confirming the relationship of IGF-1, TAO and thyroid carcinoma are necessary. References: 1. Yu et al. Thyroid-associated orbitopathy in patients with thyroid carcinoma A case report of 5 case. Medicine (2017) 2. Manzella et al Activation of the IGF Axis in Thyroid Cancer: Implications for Tumorigenesis and Treatment. International Journal of Molecular Sciences, (2019). 20 (13), 3258.
SAT-LB54 Acute Sterile Meningitis as a Primary Manifestation of Pituitary Apoplexy
Authors: Tumyan Gayane , Mantha Yogamaya , Gill Rahul , Feldman Mark
Published: May 2020

Background: Pituitary apoplexy (PA) is a rare endocrinopathy that requires prompt diagnosis and treatment. Presentation with acute neutrophilic meningitis is uncommon.

Clinical Case: A 67-year-old man presented to our hospital with a 2-week history of worsening bilateral frontal headache, nausea, and dry heaving. On admission, the patient was somnolent with a score of 13 on the GCS assessment (E2, V5, M6). The neurological exam was overall normal with normal ocular motion and intact cranial nerves, except for a left eye peripheral vision defect. Plain head CT revealed a well-circumscribed ovoid pituitary mass with suprasellar enlargement, consistent with a pituitary macroadenoma. Sellar MRI showed a pituitary mass, roughly 20 x 19 x 24 mm, bulging into the suprasellar cistern with optic chiasm elevation. Analysis of pituitary function revealed low ACTH concentration of 2.8 pg/mL (n = 7.2 - 63.3 pg/mL), a low random cortisol level of 1.7 ug/dL (n = 2.9 - 19.4 ug/dL), a low TSH of < 0.1 uIU/mL (n = 0.35 - 4.9 uIU/mL), a low free T4 level of 0.72 ng/dL (n = 0.77 - 1.48 ng/dL), a low LH of 0.8 IU/L (n = 1.7 - 8.6 IU/L) with a very low total testosterone level of < 3 ng/dL (n = 300 - 720 ng/dL) and normal prolactin, IGF-1 and GH levels. On hospital day 2, the patient had worsening encephalopathy with left eye ptosis and decreased vision. Repeat CT and MRI showed no interval change in the pituitary adenoma or evidence of bleeding. An immediate lumbar puncture was performed and CSF analysis revealed an increased leukocyte count of (1106/mm3) with 89% neutrophilic granulocytes, and increased total protein level of 138 mg/dL (n = 15 - 40 mg/dL), red blood cell count of 2040 without xanthochromia and glucose of 130 mg/dL (n = 40 - 70 mg/dL). Based on the laboratory results and new symptoms, empirical antibiotic (vancomycin, ceftriaxone, and ampicillin) therapy was started for suspected bacterial meningitis before the confirmation of the CSF culture study. CSF culture did not grow any organisms. Given the sudden visual impairment and neurological deterioration, the patient underwent transsphenoidal resection of the tumor with free nasal mucosal graft reconstruction. Histological examination revealed a necrotic pituitary adenoma with apoplexy and no evidence of hemorrhage. Postoperatively, his neurological exam greatly improved. His left pupil was reactive to light and the third palsy was improving.

Conclusion: This case reinforces the importance of including PA in the differential diagnosis of acute headache, particularly in patients presenting with visual disturbances. Patients with PA often present with sterile meningitis due to increased debris and blood in the subarachnoid space which closely mimics acute bacterial meningitis. While MRI remains a sensitive imaging modality for the detection of PA, the latter remains a clinical diagnosis. Timely diagnosis with high clinical suspicion and treatment is essential.
SUN-LB37 Atypical Presentation of Primary Adrenal Angiosarcoma With Cushing’s Syndrome - a Case Report
Authors: Cardona Zulma , Haider Yasser A , Eisenberg Yuval
Published: May 2020

Angiosarcoma is a rare aggressive malignancy originating from the endothelium of blood and lymphatic vessels, accounting for 1% of all tissue sarcomas. These tumors usually invade skin and soft tissue, however they may also invade visceral organs and bones as metastatic disease. Approximately 50 cases have been reported in the literature describing primary adrenal angiosarcomas (PAA). This case represents the first report to describe concomitant Cushing’s syndrome in the setting of epithelioid PAA. A 38-year-old female with pre-diabetes mellitus and hyperlipidemia presented to the emergency department complaining of cough with bloody sputum. Physical exam was remarkable for bilateral lower extremity edema; no Cushing’s features appreciated. Bilateral subsegmental and lobar pulmonary emboli (PE) along with lytic lesions on the ribs were found on Computed Tomography (CT) PE protocol. Chest CT Angiography to prepare for arterial embolization to treat hemoptysis, demonstrated a large heterogeneous enhancing mass arising from the adrenal gland. MRI with adrenal protocol to evaluate incidentaloma revealed an indeterminate 5.2 x 5.6 x 5.2 cm right adrenal mass with central necrosis.Biochemical evaluation revealed a nonsupressible 1mg dexamethasone suppression test (3.3 ug/dL, ref: <1.8 ug/dL), slightly elevated urine metanephrines (191 ug/d, ref: 39 -143 ug/d) and normal plasma metanephrines (0.16 nmol/L, ref: 0.0 - 0.49 nmol/L). Given the biochemical evidence of mild hypercortisolism and uncertainty of etiology of other CT findings, the decision was made to pursue adrenalectomy to aid in the presumed oncologic diagnosis. She underwent successful adrenalectomy, however the postoperative course was complicated by hypotension resistant to fluids. ACTH stimulation test revealed a baseline cortisol <1.0 (ref: 0.0-9.0 ug/dL) with an ACTH of 8 pg/mL (ref: 6 to 58pg/mL), and 60 minute post stimulation cortisol level was 5.5 ug/dL (ref: >18.0 ug/dL). She was started on hydrocortisone replacement therapy, with clinical improvement in hypotension and was eventually tapered off steroids completely.Surgical pathology identified positive staining for CD31, CD34, factor 8, CAM 5.2, and Vimentin consistent with epithelioid angiosarcoma with lymphovascular invasion. There was additionally evidence of adrenocortical hyperplasia on the tissue resected. She established care with oncology and is currently completing 8 cycles of paclitaxel for metastatic disease to bones and lungs. Our patient’s pathology results, and postoperative course suggest the presence of concomitant non-ACTH dependent Cushing’s syndrome associated with epithelioid PAA. This case highlights the importance of thorough biochemical testing before adrenalectomy in the setting of PAA given the possibility of Cushing’s syndrome, which could contribute to post-surgical complications, and prolonged hospital stays.
SUN-LB38 Adrenal Tumor Causing Unexplained Hyperhidrosis in a Young Man
Authors: Unterborn Rebecca , Bhatt Bankim
Published: May 2020

Introduction: Pheochromocytoma is a rare neuroendocrine tumor, afflicting around 0.8 out of 100,000 people per year [1]. The “classic triad” of headache, diaphoresis, and tachycardia is well documented in the literature. The “classic triad” in combination with hypertension has up to 91% sensitivity and 93.5% specificity for the diagnosis of pheochromocytoma [2]. Generalized sweating is part of the “classic triad”, however there is paucity of evidence in the literature describing diaphoresis as the only presenting symptom of pheochromocytoma.Case description: A 20-year-old male presented with five year history of worsening hyperhidrosis without any other associated symptoms. Vital signs were blood pressure of 138/82 mmHg and heart rate of 60 bpm. The remainder of the physical exam was normal. Laboratory testing showed 24 hour urine norepinephrine level of 1,002 ug/24 hours (normal: 0-135 ug/24hrs), plasma normetanephrine was 2,873 pg/mL (normal: 0-145 pg/mL) and plasma norepinephrine was 2,869 pg/mL (normal: 0-874 pg/mL). CT abdomen revealed a 4.0 x 3.1 x 4.3 cm left adrenal mass. After appropriate preoperative preparation, he successfully underwent a laparoscopic left adrenalectomy with complete resolution of diaphoresis. Pathology confirmed a completely resected pheochromocytoma.Discussion: This case reflects an atypical presentation of pheochromocytoma; a disease with high cardiovascular morbidity and mortality [3, 4]. The case demonstrates that the absence of hypertension or all three symptoms of the “classic triad” does not exclude the diagnosis of pheochromocytoma and any singular symptom of catecholamine excess warrants an evaluation for pheochromocytoma. This case report helps to establish the need to better quantify individual symptoms of patients with this disease in order to better understand the entire spectrum. Providers need to be aware of atypical presentation of this disease in order to decrease poor outcomes that can result from undiagnosed pheochromocytoma. 1. Beard, C.M., Sheps, S.G., Kurland, L.T., Carney, J.A., Lie, J.T., Occurence of pheochromocytoma in Rochester, Minnesota 1950-1979. Mayo Clinic proceedings, 1983.2. Bravo, E.L., Pheochromocytoma: New concepts and future trends. Kidney International, 1991. 40.3. Lenders, J.W.M., Duh, Q.Y., Young, W.F, et. al, Journal of Clinical Endocrinology and Metabolism. 2014.4. Zelinka, T., Petrak, O., Turkova, H., et. al, High Incidence of Cardiovascular Complications in Pheochromocytoma. Hormone and Metabolic Research, 2012.
SAT-LB3 Developing an Integrative Medicine Patient Care Protocol for Natural Fertility in Primary Infertile Couples: A Case Series
Authors: Hatzidakis Vassilia E
Published: May 2020

Background:Although advances in the field of Assisted Reproduction have improved significantly the reproductive outcome for infertile couples, success rates nonetheless remain low. Furthermore, several infertile couples are skeptical of using experimental or even established ART treatments, resulting in the need for reproductive health professionals to discuss other models which might best benefit patients who need fertility care.Clinical case series:All patients that were referred to our clinic for primary infertility (no positive pregnancy test after at least 2 years of unprotected intercourse) and had been either offered to proceed with IVF or had already a history of at least 1 failed IVF cycle, in the course of 1 year (March 2018-February 2019) were included in this study. All patients were younger than 42 years of age, AMH less than 1 ng/mL, FSH less than 12 IU/L (follicular phase FSH normal range 2.8-9.3 IU/L) and normal ovulation was present. Couples were counseled regarding a novel integrative model of achieving spontaneous pregnancy through expectant management while modifying key parameters affecting female fertility, developed after evidence-based appraisal of all relative literature. All 14 patients were examined for insulin resistance, subclinical thyroid disease, thrombophilia, and chronic endometritis and were offered the appropriate treatment, aiming for optimal (as opposed to within normal range) figures. For chronic endometritis both spouses received a one-month long triple antibiotic treatment. All patients were given careful personalized nutritional and vitamin supplementation guidelines. Regarding the psychological component of fertility all patients underwent monthly homeopathy and/or weekly acupuncture courses. All patients were designed to be followed-up for 6 months after completion of treatment (9 months after antibiotic treatment). 3 patients dropped out before receiving full treatment (rate 21%). 2 patients did not have a positive pregnancy test. All 9 remaining patients came back with a positive pregnancy test (rate 81% of those who completed treatment) on the first month of follow-up that resulted in an uncomplicated pregnancy and delivery of healthy singleton babies. Conclusion:This is the first case series indicating that expectant management could be the answer to some cases of infertility. Poor responders are sometimes reluctant to be involved in the global trend of IVF and ART, therefore a more holistic integrative approach might balance the imbalances and increase their fecundity. However, no causal inferences should be made from this consecutive case series regarding the efficacy of the investigated treatment.
SAT-LB132 3-Generation Study of Metabolic Disruption by Pregnancy Serum PFASs: Associations With Abdominal and Whole-Body Obesity in Granddaughters in a 60-Year Follow-Up of the Child Health and Development Studies Cohort
Authors: Cohn Barbara A , Krigbaum Nickilou , Cirillo Piera
Published: May 2020

Introduction. We previously found a 3.6-fold increased risk of breast cancer in daughters associated with high maternal (F0) early postpartum serum EtFOSAA combined with high F0 cholesterol (https://doi.org/10.1016/j.reprotox.2019.06.012). Here we test the hypothesis that F0 early postpartum EtFOSAA, in combination with F0 serum cholesterol predicts abdominal obesity (waist circumference > 88cm) and/or whole-body overweight or obesity (body mass index > 25 kg/m2) in daughters (F1) at age 30 and granddaughters (F2) at age 20. Methods. We measured F1 and F2 weight, height, waist circumference and blood pressure when F1 were an average age of 50 years and adult F2 were an average age of 20 years (N=213 triads). F1 also reported their weight at age 30, near the mean age of their pregnancies with their daughters (F2) to allow control for obesity during F2 gestation. EtFOSAA, PFOS, and cholesterol were assayed in archived early postpartum F0 serum samples collected within 3 days of delivery. Results. F0 cholesterol significantly (p<0.05) modified the association of F0 EtFOSAA with self-reported obesity at age 30 in F1 and measured abdominal and whole-body obesity, and blood pressure at age 20 in F2. Association patterns were similar for all outcomes: F0 EtFOSAA was associated with high metabolic risk when F0 serum cholesterol was low (Quartile 1): e.g. 20-year-old F2 had an estimated 2.3 fold increase in the joint risk of abdominal and whole-body obesity over the inter-quartile range of F0 ETFOSAA, 95% Confidence Interval= 1.1, 4.8. F0 EtFOSAA associations with F2 metabolic risk were independent of F0 race, early pregnancy overweight (BMI >25 kg/m2), and serum PFOS. F1 obesity at age 30 did not mediate F0 EtFOSAA associations with F2 outcomes, but additionally predicted high metabolic F2 risk. Conclusions. Findings support the hypothesis that in utero exposure to EtFOSAA impacts metabolic risk factors in female F2 exposed as germline and also independently via promotion of overweight in F1 (their mothers) during F2 gestation.
SUN-497 Life-Saving Management of Thyrotoxicosis with a Single Session of Plasmapheresis
Authors: Rakhra Varundeep , Patel Parth , Cabandugama Peminda K
Published: May 2020

Thyroid hormones are essential in controlling numerous metabolic and regulatory processes in the human body. Thyroid storm is a medical emergency and is the most extreme manifestation of the overproduction of thyroid hormones. It is critical to recognize thyroid storm at its earliest state and conventional practice recommends initiating treatment immediately with steroids, thionamides, and beta-blockers.Here we present a case of a patient with Graves’ disease in which thionamides could not be continued due to acute thionamide-induced hepatotoxicity. With the patient’s worsening thyrotoxic state, declining mental status and clinical deterioration; the decision was made to initiate plasmapheresis as a life-saving therapy to remove the thyroid stimulating antibodies responsible for the patient’s deteriorating status.After one session of plasmapheresis, the patients’ clinical condition began to significantly improve to baseline, along with normalization of his thyroid function and the patient was discharged home with plans for emergent thyroidectomy.This case demonstrates the importance of considering plasmapheresis as a life saving measure in the treatment algorithm of patients with extreme thyrotoxicosis and thyroid storm in which traditional therapies such as thionamides, steroids, and beta-blockers cannot be used or are ineffective. Reference:Ono, Y., Ono, S., Yasunaga, H., Matsui, H., Fushimi, K., & Tanaka, Y. (2016, February 18). Factors Associated With Mortality of Thyroid Storm: Analysis Using a National Inpatient Database in Japan. Retrieved April 6, 2019, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4998648/
SAT-LB86 Improvement In Metabolic Indices Including Thyroid HormonesVia Enhanced Absorption Of Nutrients By Teduglutide In Short Bowel Syndrome
Authors: Oba Ken C , Kabadi Udaya M
Published: May 2020

Background: Short bowel syndrome is characterized by maldigestion and malabsrption resulting in deficiencies of multiple nutrients including vitamins and minerals. Most subjects required parental elimination for survival. GLP 2 RA Teduglutide was recently approved for treatment of short-bowel syndrome especially for those requiring parenteral support. Objective: To demonstrate the utility of GLP2 Receptor Agonist Teduglutide in improvising multiple metabolic indices In presence of short bowel syndrome. Case presentation: 66-year-old Caucasian female presented with a history of short bowel syndrome and associated vitamin deficiencies, hypothyroidism requiring large dose of levothyroxine, diarrhea, and liver cirrhosis. Upon starting teduglutide the subject saw improvement in her symptoms. Moreover, daily dose of levothyroxine required reductions from 300 mcg to 150 mcg to maintain desirable serum concentrations of free T4, free T3 and TSH. Finally, serum levels of several vitamins attained greater than therapeutic concentrations requiring dosage reductions. Also notable was the improvement in her liver function tests, remission from ascites and regeneration of liver nodules. Conclusion: Herein, we report an adult subject with short bowel syndrome with concurrent hypothyroidism and multiple vitamin deficiencies who following administration of GLP2 RA therapy demonstrated a marked improvement in her metabolic parameters with some requiring reduction in daily dose along with improvement in manifestations of liver cirrhosis.
MON-LB122 Psychiatric Medication Induced Diabetes Mellitus
Authors: Khanal Bishal , Tharu Biswaraj , Tharu Sunraj , Khanal Asmita
Published: May 2020

Psychiatric medications are well established cause of diabetes. Our case had similar presentation. 67-year-old African-American male with history of hypertension and dementia was brought to the ER for auditory hallucination and bizarre behavior. His home medications were Hydrochlorothiazide, Nifedipine and Spironolactone. Psychiatry was consulted and he was admitted to psychiatric floor. He was diagnosed for first time with psychosis and depression. He was treated with citalopram 20 mg for depression; donepezil 10 mg for dementia and risperidone 0.5 mg twice a day for psychosis. 2 weeks later he developed difficulty swallowing and weakness, blood glucose level of 1263 mg/dl. All of his psychiatric medications were stopped except for citalopram 10 mg daily and patient was transferred to ICU. In the ICU, pH was 7.28 (normal 7.34-7.45), normal anion gap, bicarbonate 29mmol/L (normal 20-24), plasma osmolality 428 mOsm/kg (normal 280-320), HbA1c 10% (normal 4-5.6). He was intubated and managed as Hyperosmolar Hyperglycemic Non-Ketotic coma (HONK). He was started on insulin drip and later transitioned to Lantus and short-acting insulin. He improved and was then extubated. After 40 days, repeat A1C was 7.4%. The patient moved to another state and follow-up was lost.

Discussion While the patient was on thiazide for a long time, he had a fairly good glucose control; his A1C ranged from normal to prediabetic (A1c 5.7%-6.4%). This makes thiazide unlikely cause of diabetes mellitus for him. The fact that right after 21 days of starting psych medications caused him to land in ICU for HONK, with A1c of 10% and glucose of 1273 mg/dl, strongly suggests that this is a case of psych medications induced T2DM. This is also supported by the fact that discontinuation of those medications lowered the A1c to 7.4% in 40 days. 3 weeks before the hospitalization his A1c was 5.1%. Metformin is demonstrated to be most promising long term medication in cases like this.

Conclusion Psychiatric medications are important cause of drug induced diabetes and should always be thought as a cause of acute new onset diabetes. Stopping the offending drugs ensues good glycemic control.
SUN-LB119 Role of HNF4a Isoforms in the Carbohydrate/Lipid Switch in the Liver and Responsiveness to AMPK
Authors: Radi Sarah , Deol Poonamjot , Deans Jonathan Robert , Fekry Baharan , Eckel-Mahan Kristin , Sladek Frances M
Published: May 2020

Hepatocyte Nuclear Factor 4α (HNF4α), the master regulator of liver-specific gene expression, is regulated by two promoters (P1 and P2) which drive expression of two groups of HNF4α isoforms referred to here as HNF4α1 and HNF4α7. HNF4α is a known regulator of gluconeogenesis and is mutated in maturity onset diabetes of the young one (MODY1). Conventionally, it was thought that HNF4α1, but not HNF4α7, is expressed in the normal adult liver, with HNF4α1 downregulated and HNF4α7 upregulated in liver cancer. Now, we identify a previously undescribed role for HNF4α7 in the normal adult mouse liver - one involved in the diurnal variations of lipid and carbohydrate metabolism. More specifically, HNF4α1 appears to be a major driver of gluconeogenesis while HNF4α7 is a driver of ketogenesis: we hypothesize that alterations in the levels of the HNF4α isoforms during the day function as a molecular switch between the two. Moreover, our preliminary data show that HNF4α7 is required for increased levels of circulating ketone bodies in female mice, suggesting interactions with the estrogen pathway. AMP-Activated Protein Kinase (AMPK), an energy-sensing kinase that also plays a major role in carbohydrate and lipid metabolism, has been shown to phosphorylate HNF4α1 in vitro, but effects in vivo and on HNF4α7 are not known. In order to investigate the impact of AMPK on HNF4α isoforms, we employed HNF4α isoform-specific mice α7HMZ (express only HNF4α7) and α1HMZ mice (express only HNF4α1), as well as heterozygous mice which express both. Intraperitoneal injection of the mice with AMPK activator AICAR leads to a rapid decrease in glucose. Interestingly, half the α7HMZ males and all the females began seizing 30 min post injection, while very few α1HMZ males/females and none of the heterozygous mice seized. Moreover, there were differences in the survival of the different genotypes: a third of α1HMZ mice die within 24hrs, while two thirds of α7HMZ mice die within a week, with all heterozygous mice surviving. We suspect the seizures could be due to an electrolyte imbalance exacerbated by AICAR or extremely low glucose caused by AICAR. The α7HMZ females have significantly lower potassium levels compared to α1HMZ and wildtype mice. Additionally, AMPK is known to regulate Na+/glucose transporters, and HNF4α1 is expressed in the proximal tubules in the kidney (responsible for Na+ uptake). To elucidate the cause of the seizures, AICAR injections were repeated with α1HMZ males followed by a glucose or saline gavage. Interestingly, half of the glucose-gavaged mice died within 24hrs, while all of the saline-gavaged mice survived. Our work underscores the critical role that the HNF4α isoforms play in the metabolic switch, and suggests that the kidney as well as the liver could be involved.
MON-LB130 Glucocorticoid Receptor Signaling and Stress in the Developing Mammalian Germline
Authors: Cincotta Steven Anthony , Laird Diana
Published: May 2020

While the consequences of stress on organs such as the heart and immune system have long been established, it has only recently been shown in mice that stress experienced during pregnancy can cause molecular and behavioral changes in the exposed fetus, and even their offspring. The transmission of such phenotypes across generations implies that fetal germ cells can sense and maintain epigenetic memories of stress experienced in the womb. However, how the fetal germ cells within the developing embryo detect and respond to these stress signals is unknown. In response to stress, the major circulating hormone released is cortisol, which is the ligand for the nuclear hormone receptor known as the glucocorticoid receptor (GR). GR induces highly cell type-specific transcriptional changes in many cell types, although its function in germ cells has yet to be explored. Our preliminary studies have shown, for the first time, the robust expression and dynamic localization of GR in fetal germ cells, suggesting its activity during a crucial window of epigenetic reprogramming in male and female germ cell development. Fetal germ cells naturally undergo genome-wide demethylation of somatic and parental imprints, which leads to the de-repression of transposons that are normally silenced by methylation at their promoters. If not properly re-silenced, these transposons will generate large numbers of DNA double strand breaks during transposition, posing a serious risk to germline integrity. When GR was genetically deleted from all cells of the mouse body, we discovered elevated expression of the retrotransposon, Line1 (L1), specifically in the developing germ cells. Surprisingly, mice with a conditional deletion of GR specifically in germ cells were unable to phenocopy the full body knockout, implying that GR-mediated repression of L1 in fetal germ cells is a non-cell autonomous effect. Rather, conditional deletion of GR from the surrounding somatic cells (e.g. granulosa cells of the ovary) demonstrated increased germ cell L1 expression, strongly suggesting that GR signaling through the somatic niche is indirectly regulating L1 expression in neighboring germ cells. We therefore hypothesize that GR signaling from the somatic cell niche is functioning to indirectly suppress L1 expression within the developing fetal germ cells, which holds broad implications for how stress signals mediated by GR signaling can influence germline integrity and thus the health of future generations.
SUN-LB80 Thyroglossal Duct Cyst Carcinoma in a 12 Year Old Boy. Should Total Thyroidectomy Be Done?
Authors: Sitja Marina Mora , Montane Lucía Sentchordi , Fernández María Sanz , Berrocal Julio Cerdá , Navazo Sara de la Mata , González-Pinto Lucía Carrascón , de León Esther González Ruiz , Rodríguez Arnao Dolores , Sánchez Amparo Rodríguez
Published: May 2020

INTRODUCTION The thyroglossal duct cyst (TGDC) is the most common congenital anomaly of the neck in childhood. However, thyroid carcinoma of the thyroglossal duct cyst is rare. It occurs in less than 1% of cases and the diagnosis is usually made from histopathologic findings after cyst surgery. Papillary carcinoma is the most common histologic subtype. The management of the TGDC carcinoma is not well defined. Sistrunk procedure (resection of the cyst and hyoid bone) followed by total thyroidectomy is the classic treatment, due to frequency of concomitant thyroid cancer (20-60%). However some authors propose a more conservative management performing thyroidectomy only in certain cases (positive margins, abnormal preoperative imaging, extension of TGDC carcinoma beyond the cyst wall). Lymph node resection and radioactive iodine therapy are used on advanced stages. CLINICAL CASE A 12-year-old boy presented with a four-month history of neck swelling. There was no previous exposure to irradiation or positive family history of thyroid cancer. Physical examination revealed a 5 cm mass located in the midline region of the neck, slightly tilted to the left, above the hyoid bone, covered by normal skin. A neck ultrasound was performed showing a normal thyroid gland, and a cystic lesión compatible with a TGDC. A CT scan corroborated this finding, showing a cystic lesión of about 3.1 cm x 2.1 cm x 3.7 cm (anteroposterior, transverse and craniocaudal planes) with a small solid pole in the posterior portion of the cyst, 1x1 cm on the axial plane. Small cervical lymph nodes with no suspicious features were also described. Thyroid function tests were normal. Sistrunk operation was performed for resection of the TGDC. Histologic examination revealed papillary carcinoma in a thyroglossal duct cyst. It measured 17 mm at its maximal diameter and invaded the cyst wall 1 mm with negative margins. Consequent to the diagnosis of TGDC carcinoma, total thyroidectomy was performed on a second surgery whithout side effects. Thyroid tissue showed usual morphological features without signs of malignancy. Currently the patient undergoes levothyroxine replacement treatment.CONCLUSIONS Papillary thyroid carcinoma in thyroglossal duct cysts is rare entity and even rare in children. Given that several studies in adults show a non-negligible percentage of patients with TGDC carcinoma and a normal thyroid ultrasound who had a concomitant thyroid cancer, the most controversial part of its management is whether total thyroidectomy should be done or not. Although some groups advocate thyroidectomy only in specific cases of TGDC carcinoma, its multifocal nature and the low risk of complications of thyroid surgery in pediatric referral centers make us supporters of performing total thyroidectomy to all patients.
SUN-LB61 Differential and Opposite Regulation of Acid Labile Subunit (ALS) Versus Insulin-Like Growth Factor I (IGF-I) by Oral Estrogens in Premenopausal Women
Authors: Schilbach Katharina , Haenelt Michael , Nicolay Shiva Sophia , Schwerdt Laura , Schwaiger Rita , Benedix Sarina , Longo Schweizer Junia Ribeiro de Oliveira , Störmann Sylvère , Schopohl Jochen , Bidlingmaier Martin
Published: May 2020

Background: The impact of estrogens (E2) on the growth hormone (GH)/IGF-I axis is known to depend on route of administration: While oral E2 increases GH and decreases IGF-I, transdermal E2 has only limited or no effect. However, data concerning the impact of E2 on IGF binding protein 3 (IGFBP 3) and ALS are less clear. One study in girls demonstrated higher ALS with oral E2, while the opposite was suggested for postmenopausal women. No data are available for healthy premenopausal women.Methods: We measured IGF-I, IGFBP 3 and ALS in fasted healthy adults (93 males (M), 35 premenopausal women without E2-containing oral contraception (FPRE), 37 premenopausal women with E2-containing oral contraception (FPREOC) and 34 postmenopausal women (FPOST)). IGF-I and IGFBP 3 were measured using the IDS-iSYS chemiluminescence immunoassay, and ALS by an in-house immunofluorometric assay (limit of quantification (LoQ) < 50 mU/ml, range 50 - 4000 mU/mL).Results: Median age (range) was 33 (20 - 76), 28 (20 - 44), 24 (21 - 36) and 56 (49 - 70) years for M, FPRE, FPREOC and FPOST, respectively. As expected, IGF-I was lower in FPREOC compared to FPRE (median IGF-I xULN (IQR) 0.56 (0.45 - 0.73) and 0.72 (0.63 – 0.80), P = 0.0017, Kruskal-Wallis). ALS was significantly higher in FPREOC compared to all other groups (mean ALS in M, FPRE, FPREOC and FPOST: 636, 708, 861 and 648 mU/mL, respectively, ANOVA P < 0.0001, Dunnett’s post-hoc test: M vs FPREOC: P < 0.0001, FPRE vs FPREOC: P = 0.0007, FPOST vs FPREOC: P < 0.0001). IGFBP 3 was not different in females with and without oral E2 (median IGFBP 3 xULN (IQR) FPREOC vs FPRE: 0.62 (0.54 - 0.67) vs 0.60 (0.49 – 0.76), Kruskal-Wallis P = 0.295, Dunn’s post-hoc test: P > 0.9999). This was also true between all other groups (Dunn’s post-hoc test: P ≥ 0.4). In our adult cohort, ALS exhibited negative correlation with age (Pearson r = -0.282, P = 0.0003), similar to IGF-I and IGFBP 3. While IGF-I exhibited a moderate negative correlation to BMI (Pearson r = -0.25, P = 0.0013), IGFBP 3 and ALS were not significantly related to BMI.Conclusion: While IGF-I, IGFBP 3 and ALS all are known to be secreted in response to GH, and IGF-I and ALS are assumed to be produced by the same cells in the liver (hepatocytes), the three GH dependent biomarkers appear to be differently regulated by metabolic factors and oral E2. Only IGF-I has some modest association with BMI. Oral E2 is associated with reduced IGF-I, unchanged IGFBP 3 but increased ALS. While the mechanism behind the differential regulation remains to be uncovered, E2 therapy must be taken into account when interpreting IGF-I and ALS concentrations.
MON-LB6 Association Between Sex Steroid and Metabolic Parameters in Cord Blood With Placental Fatty Acid Transporter in Obese Pregnant Women
Authors: Maliqueo Manuel , Álvarez Daniela , Ortíz Macarena , García Madian , Flores Cristian , Echiburú Bárbara , Crisosto Nicolás
Published: May 2020

Obesity reduces maternal insulin sensitivity and alters sex steroid serum concentrations. However, it is not clear if these changes are reflected in the fetal circulation. On the other hand, similar to other metabolic tissues, modifications in sex steroid concentrations and metabolic parameters could modify the transport and metabolism of fatty acids (FA) in the placenta increasing their availability for the fetus. Therefore, we aimed to study, in pregnant women with normal-weight and obesity, sex steroid serum concentrations in cord blood and their relationship with the gene expression of FA transporters and of molecules related with FA metabolism in the placenta. We included 26 pregnant women with normal-weight and 26 pregnant women with obesity without pregnancy complications. At term of pregnancy, mixed cord blood and placenta samples were collected and stored at -80°C. Serum concentrations of dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), androstenedione, testosterone, estrone, estradiol, estriol, insulin and TNF-α were measured by RIA or ELISA. Glycemia and lipid profile were also analyzed. In placental samples, the gene expression of MFSD2A, CD36, FABP4, SLC27A4, PPARG, LPL and DGAT were determined by quantitative PCR. No differences were observed in sex steroid concentrations and metabolic parameters between groups. On the other hand, the gene expression of MFSD2A, CD36 and FABP4 were higher in placentas from women with obesity compared to women with normal-weight (P = 0.050, P = 0.037 and P = 0.038, respectively). When distributed according to fetal sex, cholesterol levels were higher in cord blood of women with obesity and female fetuses (P = 0.005), whereas glycemia was lower in women with obesity and male fetuses (P = 0.045). In turn, the gene expression of CD36 and FABP4 were higher (P = 0.024 and P = 0.034, respectively), whereas MFSD2A tended to be higher (P = 0.092) only in placentas from women with obesity and male fetuses. Moreover, in women with obesity and male fetuses, glycemia was positively correlated with MFSD2A (r = 0.650; P = 0.022), and in women with obesity and female fetuses FABP4 was inversely correlated with triglyceride levels (r = -0.580; P = 0.048). In conclusion, these data suggest that modifications in placental steroidogenesis do not affect sex steroid serum concentrations in the fetal circulation. On the other hand, metabolic parameters in cord blood of pregnant women with obesity are associated with an abnormal expression of FA transporters in placental tissue.
SAT-LB78 TSH Is a Negative Modulator of Hippo Transcriptional Effectors
Authors: Fernández-Méndez Celia , Santisteban Pilar
Published: May 2020

Hippo signaling pathway regulation by hormonal signals acting through G-coupled receptors has been widely described. Modulation of processes such as tissue growth or differentiation by this pathway critically relies on the location and levels of its major effectors: the cofactors YAP/TAZ and the family TEAD of transcription factors. Despite this well-defined regulatory mechanism, little is known about the Hippo pathway in the thyroid gland. Thyrotropin (TSH), main factor for thyroid follicular cells differentiation, plays its role by interacting with its G-protein-coupled receptor (TSHR). High serum TSH levels are associated with hypothyroidism, characterized by a change in thyroid follicle morphology and inflammation of the thyroid gland. This led us to study if TSH could modulate the Hippo pathway.Rat thyroid follicular cells (PCCl3) were treated with TSH and forskolin, an adenylyl cyclase activator. By immunofluorescence and western blot, levels and subcellular location of the Hippo Pathway components were assessed in different conditions. An increase of the Hippo kinase MST1/2 and LATS1/2 was observed after TSH and forskolin treatments, corresponding to a downregulation of the transcriptional mediators of the pathway TAZ, YAP and Tead1. Especially remarkable is the translocation of YAP/TAZ from the nucleus, which involves a decrease in their activity.Next, we validated the results in an in vivo model generating hypothyroidism in 3-month-old male C57BL/6J by adding MMI (2-Mercapto-1-Methylimidazole) and perchlorate (KClO4) to their drinking water. After 2 weeks of treatment, we euthanized the animals, validated higher TSH serum levels and performed analysis of the Hippo components in the thyroid by immunohistochemistry. A reduction in the levels of the Hippo effectors TAZ, YAP and Tead1 was found in the thyroid slices from hypothyroid mice, confirming the in vitro results. In addition, evaluation of a human thyroid tissue microarray, including Hashimoto disease samples, led to a validation of the previously described TSH role.Hereby, we report a crosstalk by which TSH is increasing the kinase axis of the Hippo pathway thus decreasing the activity of its main transcriptional effectors in the nuclei. Future research of the role of these transcriptional effectors will be carry out to discern if their decrease could be associated with the morphology changes linked to hypothyroidism.