bluuebunny/crossref_metadata_2025 huggingface dataset:
MON-LB304 The Construction of the Online Health Guidance Service for Life-Style Related Diseases (Kanazawa Slim Study)
Authors: Kometani Mitsuhiro , Oka Rie , Yasugi Ayaka , Gondo Yuko , Nomura Akihiro , Aono Daisuke , Higashitani Takuya , Karashima Shigehiro , Usukura Mikiya , Furukawa Kenji D , Yoneda Takashi
Published: May 2020

Background: Metabolic syndrome is a cluster of metabolic disorders including elevated blood pressure, high plasma glucose, excess body fat around the waist, and abnormal cholesterol or triglyceride levels. These conditions cause serious complications such as heart disease, stroke and type 2 diabetes. In Japan, specific health checkups and specific health guidance which focused on metabolic syndrome has been performed since 2008. Those who fall under certain criteria need to receive a medical treatment guidance from doctor, public health nurse or dietitian. Those who received health guidance receives a reassessment of improvement of their life-style 3-6 months later. However, the efficacy of this approach has not been elucidated. In addition, many persons who have metabolic syndrome do not receive this instruction. Recently, the image analysis technology using the artificial intelligence (AI) progresses rapidly. The smart device application “Asken” has an AI-powered photo analysis system which analyzes the photo of the entire meal, and delivers individualized messages and dietary feedbacks. In this study, we utilized the Internet of Things (IoT) device which includes Asken app, body composition analyzer and sphygmomanometer that can connect wirelessly. Objective: Our aim is to assess the efficacy of specific health guidance adding on IoT device. This is a multicenter, unblinded, non-randomized controlled study. Results: At the end of January 2020, we recruited 219 participants including 105 participants with IoT devices. We used 48 participants (32 with IoT and 16 without IoT) who had finished a reassessment 3 to 6 months after initial guidance. Results: Age, body weight (BW), body mass index (BMI), blood pressure (BP), fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), total cholesterol (T-Chol), high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), non-HDL cholesterol (n-HDL), and triglyceride (TG), did not differ between IoT-use and control group. 6 months after initial guidance, the quantity of decrease of BW in IoT-use group was significantly larger than control (-2.5 ± 4.1 kg vs. 0.6±4.4, p = 0.03). In addition, the quantities of decrease of both T-Chol and n-HDL in IoT-use group were also significantly larger than control (T-Chol, -5.9 ± 32.0 vs. 14.3 ± 31.6, p = 0.02; n-HDL, -7.6 ± 29.0 vs. 9.4 ± 27.5, p = 0.01). Conclusion: Using IoT device might be useful for body weight loss and the improvement of mild hypercholesterolemia in those with metabolic syndrome.
SAT-LB43 Allgrove’s: A Syndrome for the “A”ges
Authors: Bailey Richard , Nyquist Alexandra , Broome David Tyler , Zimmerman Robert S , Makin Vinni
Published: May 2020

Allgrove’s syndrome is an inherited condition caused by mutations in the AAAS gene (encoding the protein ALADIN) and is inherited in an autosomal recessive pattern (1). It classically is characterized by three specific features: achalasia, Addison’s disease, and alacrima (reduced or absent ability to secrete tears). This has led to the name “Triple A syndrome”, and some have suggested a 4th ‘A’ of autonomic disturbance (2). It is important to note that the phenotype of this condition is variable, and some patients may have all three (or four) of the manifestations at initial presentation, and that other patients may develop or have worsening of the ‘As’ over time. In this clinical vignette, we present a patient with Allgrove’s syndrome who developed clinical manifestations of the third ‘A’ of Addison’s disease later in life. A 46-year-old female patient presented to our tertiary referral center for follow-up of Allgrove’s disease after having been diagnosed with genetic testing as an adolescent. Prior to presentation, she underwent esophagectomy in 1995 and additionally had confirmed alacrima with ophthalmology. She was undergoing annual surveillance testing with 8 am cortisol and ACTH stimulation testing to monitor for the development of adrenal insufficiency. Prior to consultation, her baseline cortisol was 8.7 ug/dL. At presentation and the age of 46, her ACTH stimulation test (0.25 mg cosyntropin, 3 timepoints) was positive for adrenal insufficiency with a baseline cortisol of < 0.5 ug/dL (8 am), with 30-minute value of 4.4 ug/dL and 60-minute value of 6.3 ug/dL (peak). She was started on replacement dosing of hydrocortisone 20 mg at 8 am and 10 mg at 2 pm, in addition to calcium and vitamin D supplementation. Of note, her adrenal antibody (21-hydroxylase antibodies) were negative on two separate occasions. Allgrove’s syndrome is a rare condition described by the development of three, or at times four, characteristics with support of genetic testing. This case demonstrates that patients with Allgrove’s syndrome can present with two clinical manifestations of the condition (alicrima and achalasia) and develop the third (adrenal insufficiency) later in life. Therefore, regular screening for the missing clinical manifestation of this disease should be considered. References: 1. National Institute of Health: Genetic and Rare Disease Information Center. Triple A Syndrome. Genetics Home Reference. February 2010; http://ghr.nlm.nih.gov/condition/triple-a-syndrome. Accessed 2/1/2020. 2. Kimber J, McLean BN, Prevett M, Hammans SR. Allgrove or 4 “A” syndrome: an autosomal recessive syndrome causing multisystem neurological disease. J Neurol Neurosurg Psychiatry. 2003;74:654-657.
MON-LB65 Lithium: The Culprit of Multiple Endocrinopathies
Authors: Yau Alice , Bahtiyar Gul , Rodriguez Giovanna , Martinez Escudero Jose R
Published: May 2020

Background: Lithium, commonly used to treat various psychiatric disorders such as bipolar disorder, can cause acute toxicity that presents with nausea, vomiting and diarrhea. Lithium can also cause life-threatening endocrine abnormalities, including hypercalcemia, hypernatremia, and both hypo- and hyperthyroidism.

Clinical Case: A 61-year old female with hypothyroidism, bipolar disorder, hyperparathyroidism with two-gland parathyroidectomy on lithium for over 30 years presented with altered mental status.

Initial labs revealed elevated creatinine 1.92 mg/dL (0.8-2.00mg/dL) compared to baseline 0.82 mg/dL, sodium 154 mg/dL (135-147 mg/dL), Corrected calcium 11.7 mg/dL (8.5-10.5 mg/dL), PTH 96 pg/mL (15-65 pg/mL), and high lithium levels 1.45 mmol/L (0.60-1.20 mmol/L). Further studies showed hypotonic polyuria with no increase in urine osmolality after desmopressin, consistent with nephrogenic diabetes insipidus. Lithium was held and she was treated with aggressive intravenous hydration with dextrose 5% water.

Hypercalcemia is thought to result from increased secretion of PTH due to an increased set point at which calcium suppresses PTH release; this often resolves once lithium is stopped. Lithium can also unmask previously unrecognized mild hyperparathyroidism, and/or raise serum PTH concentrations independent of calcium levels.1 The drug interferes with the kidneys’ ability to concentrate urine in the collecting tubules by desensitizing response to antidiuretic hormone, causing diabetes insipidus. The resulting volume depletion from excessive urinary water loss in turn lead to acute kidney injury and hypernatremia.2 Hypothyroidism results from lithium-inhibited synthesis and release of thyroid hormones and decreases iodine trapping.

Conclusion: Although these are infrequent complications of lithium use, they remain pertinent clinical findings to consider due to their morbidity. In this case, our patient may have avoided multiple chronic electrolyte abnormalities leading to altered mental status if lithium toxicity had been recognized earlier.

References:1. García-Maldonado, Gerardo, and Rubén de Jesús Castro-García. “Endocrinological Disorders Related To The Medical Use Of Lithium. A Narrative Review”. Revista Colombiana De Psiquiatría (English Ed.), vol 48, no. 1, 2019, pp. 35-43. Elsevier BV, doi:10.1016/j.rcpeng.2018.12.005.

2. Tasci, E. “Lithium-Induced Nephrogenic Diabetes Insipidus Responsive To Desmopressin”. Acta Endocrinologica (Bucharest), vol 15, no. 2, 2019, pp. 270-271. ACTA Endocrinologica Foundation, doi:10.4183/aeb.2019.270.
SAT-LB134 Aging Related Changes in Sex Hormone-Binding Globulin in Men With HIV
Authors: Dias Jenny Pena , Haberlen Sabina , Dobs Adrian , Lake Jordan , Palella FranK J , Kingsley Lawrence , Basaria Shehzad Sultan , Price Jennifer C , Budoff Matt , Thio Chloe L , Brown Todd Tarquin
Published: May 2020

Background: Sex hormone-binding globulin (SHBG) is a glycoprotein that regulates the bioavailability of sex hormones, may directly affect glucose metabolism, and increases with age in the general population. SHBG concentrations are higher in people with HIV, a population in whom accelerated aging has been hypothesized. It is unclear whether age-related trajectories of SHBG differ by HIV serostatus. Methods: SHBG was measured in 182 men with HIV (MWH) and 267 men without HIV (MW/oH) from the Multicenter AIDS Cohort Study (MACS) in four U.S. cities, who had ≥2 samples over a 10 year period. Outcome measure: SHBG, log2SHBG. Multivariable linear mixed-effects regression models were used to evaluate whether SHBG (log2-transformed) and its rate of change differed by HIV serostatus after adjustment for covariates: age, race, BMI, smoking, education, hepatitis C virus infection, total testosterone concentrations, time of day of blood drawn and comorbidities (history of diabetes, kidney disease, liver disease, cancer, depression, hypertension) Results: At baseline, mean age among MWH was similar to MW/oH (51±5 vs 49±6 years). However, SHBG values were higher in MWH compared to MWo/H (65.6±48.8 nmol/L vs. 45.4±22 nmol/L, p<0.001). The rate of SHBG change with age was (1.021 (95% CI:1.010-1.028) or 2.1% per year in MWH and (1.014 nmol/L/year (95% CI:1.010-1.019) or 1.4% per year in MW/oH, p=0.05 for difference in slopes. Among MWH, higher SHBG levels were significantly associated with lower CD4+ T cell count (0.99 (5%CI:0.98-1.00), p<0.05), fewer cumulative years on zidovudine (0.98 nmol/L (95%CI:0.96,1.00), p<0.001) and greater cumulative years on non-nucleoside reverse transcriptase inhibitors drugs (1.02 (95%CI:1.00,1.04), p<0.05). Conclusion: Aging-related increases in SHBG were greater in magnitude among men with HIV and were related to poorer immunologic status and antiretroviral factors. The mechanisms and consequences of these findings require further investigation.
SUN-LB135 Estrogen Receptor Beta Inhibits NFkB Signaling to Inhibit Triple Negative Breast Cancer
Authors: Aspros Kirsten , Subramaniam Malayannan , Ye Zhenqing , Sun Zhifu , Ingle James , Goetz Matthew , Hawse John
Published: May 2020

Triple Negative Breast Cancer (TNBC) affects approximately 15-20% of BC patients, yet accounts for a disproportionately higher rate of BC morbidity and mortality, in part due to lack of targeted therapies. We have shown that estrogen receptor beta (ERβ) is expressed in approximately 20% of TN breast tumors and that ligand-mediated activation of ERβ with estradiol (E2) or ERβ-selective agonists decreases tumor cell proliferation, invasion and migration in vitro and in vivo. Therefore, we aimed to elucidate the mechanisms by which ERβ elicits its anti-cancer effects in TNBC. RNAseq analysis of ERβ-expressing MDA-MB-231 cells demonstrated that ERβ significantly downregulates NFκB signaling in the presence of E2. ChIPseq for ERβ in these cells revealed that ERβ primarily associated with estrogen response elements, but 12% of all ERβ binding sites were located at NFκB consensus motifs. Using an NFκB reporter construct and qPCR, ERβ was shown to block TNFα-mediated induction of NFκB signaling and NFκB target gene expression. RNAseq analysis of MDA-MB-231-ERβ cells treated with TNFα or E2+TNFα revealed substantial global inhibition of TNFα regulated genes in the presence of E2. ChIPseq for NFκB demonstrated that ERβ significantly alters NFκB’s cistrome whereby it can both diminish NFκB binding and redistribute NFκB throughout the genome. ChIPseq also demonstrated that ligand-mediated activation of ERβ significantly diminished an activating histone mark (H3K27Ac) at many of these NFκB target genes while enhancing a repressive mark (H3K27Me3). The addition of H3K27Me3 at these loci was shown to occur through the recruitment of the histone methyltransferase, EZH2. Drug-mediated blockade of EZH2 activity reversed suppression of NFκB target gene expression by ERβ. Knockdown of NFκB or Mutation of ERβ’s DNA binding domain rendered ERβ incapable of associating with DNA, recruiting EZH2, methylating NFκB target gene loci, repressing NFκB target gene expression and inhibiting proliferation. Interestingly, ERβ was shown to elicit more potent anti-cancer effects in TNBC cells expression a constitutively active form of NFκB. These finding suggest that a primary mechanism by which ERβ functions as a tumor suppressor is through inhibition of NFκB pathway activity. Our studies have also revealed that ERβ functions as a molecular switch for EZH2 and repurposes it for tumor suppressive activities, as EZH2 has previously been reported to enrich NFκB signaling in TNBC. These findings could address the paradox that high EZH2 expression is associated with worse TNBC patient outcomes, while high H3K27Me3 expression is associated with improved patient outcomes. Currently, a Mayo Clinic Breast Cancer SPORE prospective phase II clinical trial is underway to investigate the efficacy of estradiol for the treatment of metastatic ERβ+TNBC and to further evaluate the cross-talk between ERβ, EZH2 and NFκB signaling.
SUN-LB81 Coexisting Malignant Struma Ovarii and Cervical Follicular Variant Papillary Thyroid Carcinoma
Authors: Rind Jubran Afzal Khan , Saeed Zeb Ijaz
Published: May 2020

A 44-year-old woman presented with left lower quadrant abdominal pain for 2 months. Further evaluation revealed a left adnexal mass and she underwent a TAH-BSO. A 12 cm mass arising from the left ovary was resected which on microscopy appeared to be papillary thyroid carcinoma follicular variant arising from a mature teratoma (struma ovarii). A thyroid ultrasound showed two subcentimeter right thyroid nodules without any concerning lymphadenopathy. A total thyroidectomy was then performed to allow her to receive adjuvant RAI. The cervical thyroid pathology showed a 0.6 cm follicular variant papillary thyroid carcinoma with negative margins without angioinvasion, lymphatic invasion or extrathyroidal extension. Thyroid hormone suppression with levothyroxine was started. Preoperatively, thyroglobulin was 1381 ng/ml (nl range 1.3-31.8 ng/ml). After TAH-BSO and thyroidectomy, thyroglobulin was undetectable and so was the anti-thyroglobulin antibody. With an undetectable thyroglobulin level, it was decided not to pursue adjuvant RAI and continue TSH suppression with levothyroxine. Simultaneous existence of malignant struma ovarii and cervical papillary thyroid cancer is rare and has a favorable prognosis compared to metastasis to the ovaries from primary cervical thyroid papillary carcinoma. Due to the rarity of this condition, management is not clear or well supported by evidence. Various approaches are suggested by different authors, including thyroidectomy after resection of malignant struma ovarii to facilitate adjuvant RAI, only performing surgical resection of the ovarian tumor in the absence of high risk features or performing thyroidectomy and RAI only in metastatic or recurrent disease.

References:1.Aaron Leong, Philip J. R. Roche, Miltiadis Paliouras, Louise Rochon, Mark Trifiro, Michael Tamilia, Coexistence of Malignant Struma Ovarii and Cervical Papillary Thyroid Carcinoma, The Journal of Clinical Endocrinology & Metabolism, Volume 98, Issue 12, 1 December 2013, Pages 4599-46052.Synchronous malignant struma ovarii and papillary thyroid carcinoma Pablo Fernández Catalina,Antonia Rego Iraeta, Mónica Lorenzo Solar, Paula Sánchez Sobrino DOI: 10.1016/j.endoen.2016.08.006
SUN-614 Prediction of Hypertension, Diabetes and Fractures in Eucortisolemic Women by Measuring Parameters of Cortisol Milieu
Authors: Chiodini Iacopo , Morelli Valentina , Aresta Carmen , Gaudio Agostino , Eller-Vainicher Cristina , Zhukouskaya Volha V , Merlotti Daniela , Orsi Emanuela , Barbieri Anna Maria , Fustinoni Silvia , Polledri Elisa , Gennari Luigi , Falchetti Alberto , Carnevale Vincenzo , Persani Luca , Scillitani Alfredo
Published: May 2020

Purpose. Cortisol secretion, peripheral activation and sensitivity seem to be associated with hypertension (HY), type-2 diabetes (T2D) and fragility fractures (FX) even in eucortisolemic subjects. The aim of the present study was to determine the cut-off(s) of the parameters of cortisol secretion and peripheral activation for predicting the presence of HY, T2D and FX (comorbidities). Methods. In 206 postmenopausal females (157 with ≥1 comorbidities and 49 without any), we assessed the ratio between 24-hour urinary free cortisol and cortisone (R-UFF/UFE, cortisol activation index), cortisol after 1mg-overnight-dexamethasone (F-1mgDST, cortisol secretion index), and the GC receptor N363S single-nucleotide polymorphism (N363S-SNP, cortisol sensitivity index). Results. The cut-offs for F-1mgDST and R-UFF/UFE set at 0.9 μg/dL (Area Under the Curve, AUC 0.634±0.43, p=0.005) and 0.17 (AUC 0.624±0.5, p=0.017) respectively, predicted the presence of ≥1 comorbidities. The presence of F-1mgDST >0.9 μg/dL plus R-UFF/UFE >0.17 showed 82.1% specificity for predicting the presence of ≥1 comorbidities, while the simultaneous presence of F-1mgDST ≤0.9 μg/dL and R-UFF/UFE ≤0.17 showed 88% sensitivity for predicting the absence of comorbidities. The F-1mgDST >0.9 μg/dL or R-UFF/UFE >0.17 was associated with 2.8 and 2.1 fold increased risk of having ≥1 comorbidities, respectively. The F-1mgDST ≤0.9 μg/dL plus R-UFF/UFE ≤0.17 or F-1mgDST >0.9 μg/dL plus R-UFF/UFE >0.17 was associated with 2.8 fold reduced or 4.9 fold increased risk of having ≥1 comorbidities regardless of age, BMI and N363S-SNP. Conclusions. F-1mgDST >0.9 μg/dL and R-UFF/UFE >0.17 may be used for predicting the presence of ≥1 among HY, T2D and fragility FX.
SUN-LB82 Coexistence of Medullary Thyroid Cancer With Graves Disease: A Case Report
Authors: Okoli Ogochukwu , Resta Christine A
Published: May 2020

A 59 year old woman presented with enlarged thyroid, weight loss, and hot flushes. She had previously been treated for a thyroid problem in 2013 but was lost to follow up.

On exam, she had a diffusely enlarged thyroid gland, without distinct nodule. She had brisk DTR’s and mild tremor. Lab results confirmed hyperthyroidism:TSH <0.01 mIU/L (0.27 to 4.2) FT4 2.4 ng/dL (0.9 to 1.8) FT3 7.95 pg/mL (1.8 to 4.6). TSI was 307 % (<140%).

Thyroid ultrasound showed a few sub-centimeter nodules, and 2 clinically significant nodules on the right--1.5 x 1.2 x 1.4 cm, cystic with calcifications; and 1.3 x 0.7 x 1.2 cm hypoechoic. I-123 thyroid uptake/scan showed 61% uptake and 2 right sided cold nodules. FNA biopsy showed medullary thyroid carcinoma (MTC) with staining positive for calcitonin and negative for thyroglobulin. CT thyroid showed no adenopathy. Serum calcitonin was 71 pg/mL (<5), and CEA was elevated 5.4 ng/mL (<2.5). Work up was negative for pheochromocytoma and hyperparathyroidism.After pretreatment with methimazole, she underwent total thyroidectomy with bilateral TE groove dissection. Surgical pathology confirmed MTC pT1b pN1a. She was started on levothyroxine therapy post operatively.

Discussion There are multiple reports of thyroid carcinoma (papillary and follicular) in Graves disease, but rarely MTC.1 A recent systematic review reports only 21 total cases of MTC in patients with hyperthyroidism, of whom 15 had Graves disease.2 MTC is derived from C-cells from the thyroid gland rather than from follicular cells. TSI, therefore, should not influence development or growth of MTC. Coexistence of the two conditions is likely coincidental rather than causative.

ConclusionThyroid nodules in patients with Graves should be worked up as there is a possibility of co-existing thyroid carcinoma. This patient had hyperthyroidism with cold nodules on nuclear scan corresponding to sonographic nodules. Based on these results, she had biopsy leading to diagnosis of MTC. Follow up surgery lead to diagnosis of MTC at earlier stage and provided treatment for both conditions.

References1. Staniforth, J. U. etal (2016). Thyroid carcinoma in Graves’ disease: a meta-analysis. International Journal of Surgery, 27, 118-125.

2. Sapalidis, K. etal (2019). A Rare Coexistence of Medullary Thyroid Cancer with Graves Disease: A Case Report and Systematic Review of the Literature. The American journal of case reports, 20, 1398
SUN-LB90 Taurine Reverses Protein Malnutrition-Induced Endothelial Dysfunction of Pancreatic Vasculature
Authors: Guizoni Daniele Mendes , Freitas Israelle Netto , Victorio Jamaira Aparecida , Carneiro Everardo Magalhaes , Davel Ana Paula
Published: May 2020

Background: Pancreatic islets are highly vascularized and there is a correlation between endocrine pancreas function and pancreas perfusion. Protein malnutrition during early stages of development predispose to cardiovascular diseases, impaired insulin secretion and, type 2 diabetes. However, it is unknown if there are alterations in the pancreatic vasculature in response to malnutrition. Taurine (TAU) supplementation has been suggested as antihypertensive and improves endothelial function and insulin secretion in cardiometabolic disorders. Here, we investigated the effect of TAU in the vasorelaxation and endothelium-derived factors of the lieno-pancreatic artery from protein malnourished mice. Because lieno-pancreatic artery provides blood supply to pancreatic splenic lobe, a protective effect of TAU may result in cardiometabolic benefits. Methods: Post-weaned male C57Bl/6 mice fed a normal- (14%, NP) or a low-protein (6%, LP) diet for 90 days. Concomitantly, half of LP mice received 2.5% TAU in drinking water. Lieno-pancreatic artery (internal diameter ~ 160 µm) was isolated and concentration-response relaxation curves to acetylcholine (ACh), nitric oxide (NO)-donor (SNP), or hydrogen sulfide (H2S)-donor (NaHS) were performed. The involvement of NO and endothelium-derived hyperpolarization (EDH) in ACh-induced relaxation was assessed using L-NAME (NO synthase inhibitor) or KCl (to attenuate K+ efflux), respectively. Protein expression was evaluated by Western-blot; NO and H2S production by DAF-2A and WSP-1 fluorescence, respectively. Results: Endothelium-dependent relaxation to ACh was reduced in lieno-pancreatic artery from LP compared with NP group. Either KCl or L-NAME reduced ACh-induced relaxation, but only KCl abolished differences between LP and NP, suggesting that EDH rather than NO is involved in the impaired endothelium-dependent relaxation of LP. In accordance, relaxation to SNP, NO production, and endothelial NO synthase (eNOS) expression were not altered in lieno-pancreatic artery of LP group compared to NP. Because H2S has been demonstrated to have EDH activity in several blood vessels we investigated this pathway. H2S production and NaHS-induced relaxation were both reduced in lieno-pancreatic artery of LP group compared with NP. TAU treatment reversed the impaired relaxation to ACh and to NaHS, as well as significantly increased H2S production in lieno-pancreatic artery of LP group. Conclusion: Protein malnutrition resulted in endothelial dysfunction of lieno-pancreatic artery associated with an impaired production and relaxation to H2S, which was restored by TAU. Therefore, beneficial effects of TAU on lieno-pancreatic artery vasodilatory function may result in improved pancreatic islet blood flow highlighting the potential of TAU for vasculo-metabolic protection.Funding: FAPESP, CAPES.
SUN-LB92 The Importance of Early Diagnosis and Treatment of Primary Aldosteronism on the Progression of Chronic Kidney Disease, Compared With Essential Hypertension: A Retrospective Cohort Study
Authors: Lim Jayoung
Published: May 2020

Introduction: Primary aldosteronism(PA) has few clinical phenotypes and features, compared with other endocrine hypertension(HTN). Even though hypokalemia is a typical sign of PA, most of PA reveals normal potassium concentration. For that reason, PA is likely to undetected and underestimated and it may account for larger proportion of total HTN than we expected. However, it has known that PA has higher risk of renal complications than essential hypertension(EH) and has been controversy which treatment between medication and operation is better for renal protection of PA. Methods: We retrospectively reviewed the medial records of patients with PA and EH of a single medical center from January, 2009 to December, 2019. PA patients were divided into medical and surgical treatment groups. EH patients were distinguished from one that satisfied with case detection test, called non-confirmed PA. We excluded cases with other secondary HTN and baseline eGFR < 60 mL/min/1.73m2. Results: Patients with PA(N=66) and patients with EH(N=514) were selected for analysis. Each baseline mean eGFR of patients with PA and EH indicated 91.2 ± 74.5 and 87.1 ± 19.7 mL/min/1.73m2 and statistically insignificant differences(P = 0.1688) as well as baseline SBP(P = 0.5403) and DBP(P = 0.8691). However, in spite of treatment of PA and controlled BP, mean eGFR of PA patients was lower than one of EH patients and its difference was statistically significant showing 66.5 ± 14.2 and 94.6 ± 195.9 mL/min/1.73m2 (P < .0001) at 2~ 5 years, 52.4 ± 17.9 and 77.6 ± 20.6 mL/min/1.73m2 (P < 0.0004) at 6~10 years. Baseline mean eGFR of PA with normokalemia and hypokalemia respectively were 77.7 ± 11.6 and 98.9 ± 92.5 mL/min/1.73m2 (P = 0.0269). Baseline mean eGFR of non-confirmed PA and EH were 82.5 ± 13.2 and 88.4 ± 21.1 mL/min/1.73m2 (P = 0.0240). Although baseline mean eGFR of PA with surgical treatment was better than one with medical treatment, it was reversal after 2~5 years indicating mean eGFR of PA patients treated with operation, 62.9 ± 16.1 mL/min/1.73m2 and one treated with spironolactone, 70.5 ± 12.6 mL/min/1.73m2 (P = 0.0010). Conclusions: This study support PA has worse effects on renal function than EH. PA is frequently unsuspected and undiagnosed because it hardly shows symptoms and signs. Many cases do not reveal main characteristics such as uncontrolled HTN and hypokalemia, so that patients with PA maybe have longstanding exposure to risk of CKD. Therefore it is necessary to do case detection test and rule out PA in initial hypertensive patients. In addition, more longitudinal study and research should be performed to decide personalized and adequate treatments for PA patients.
SUN-LB116 Improved Family Medicine Resident Diabetes Care Through Participation in a Diabetes Clinic
Authors: Douthitt Key , Taylor Wanda , Jonathan Piercy , Fletcher-Jones Crystal , Hughes Juanita , Slone Melissa , Feltner Frances , Atkins Robert
Published: May 2020

As the population ages and the prevalence of diabetes increases, the demand for endocrinology services, especially in underserved areas, will continue to exceed availability. Primary care residency training programs must prepare residents to care for high risk patients with diabetes who cannot access specialists. We hypothesized that resident participation in an inter-professional diabetes clinic run by primary care physicians would lead to improved diabetes care in resident patient panels.

A diabetes clinic was created in an existing primary care practice at a Federally Qualified Health Center in Eastern Kentucky. All non-pregnant, adult, Type II diabetes patients with a HgbA1C of 8.0% or greater were invited to participate in the clinic. Initial visits included evaluations by a dentist, mental health counselor, social worker, nutritionist, primary care provider, and pharmacist. Four first-year and four second-year family medicine residents rotated through the diabetes clinic and followed the patients as they saw each member of the health care team. On follow-up visits, a resident served as the primary care provider for each patient and participated in post-clinic meetings of the entire healthcare team. Resident patient charts were reviewed 3 months prior to the year-long intervention and data collected was compared to resident patient charts 3 months following the intervention.

Ninety patients served as the pre-intervention sample and 108 were in the post-intervention sample. Chi-square analysis showed a statistically significant increase in patients with A1C less than 8.0% pre (57.7%) to post (71.3%) p=0.0468. Overall, there were significant increases in all health-associated behaviors. Patients receiving eye exams increased from pre (29%) to post (66%) intervention significantly; z=-5.2, P<.001. Patients receiving a urine microalbumin test increased from pre (61%) to post (82%) intervention; z=-3.2, P<.001. Patients receiving dietary counseling increased from pre (54%) to post (79%) intervention; z=-3.6, P<.001. Patients receiving foot exams increased from pre (34%) to post (48%) intervention, z=-1.9; p=.03.

Resident involvement in a multidisciplinary diabetes clinic led by primary care physicians resulted in a statistically significant increase in HgbA1Cs < 8 among patients in their regular clinic and resulted in a statistically significant increase in their diabetic patients receiving eye exams, dietary counseling, foot exams, and urine microalbumin tests. This study suggests that teaching family medicine residents important diabetes care skills with an inter-professional team approach through the use of a diabetes clinic may be superior to standard educational practices.
SUN-LB47 Extended Release Octreotide Pharmacokinetics in Healthy Subjects After Subcutaneous Injection of MTD201
Authors: Seaman Paul , Damment Stephen J P , Kalinov Krassimir , Cook Craig , Kolev Emil
Published: May 2020

An open-label, randomised, single-dose Phase I study in healthy subjects evaluated octreotide pharmacokinetics after deep-intramuscular (IM) or subcutaneous (SC) injection of MTD201 (30mg). All subjects received Sandostatin® (100μg immediate release; SIR) by deep SC injection 24h before MTD201. MTD201 is manufactured by Q-Sphera™ printing technology to minimize particle size variation and afford simpler reconstitution and less painful injection via a 21G needle. Plasma octreotide concentrations were measured over 63 days to ascertain the potential for a 6- to 8-week dosing interval. MTD201 is being developed as a next generation long-acting somatostatin analogue for maintenance management of acromegaly and neuroendocrine cancer patients. Methods: 28 healthy subjects were randomised to two groups. The reference product SIR (100μg) was injected SC, followed 24 hours later by MTD201 administered by either IM (n=14, 38mm 21G needle) or SC (n=14, 16mm 21G needle) injection. MTD201 was resuspended in WFI to give a final injection volume of 1.5mL. Plasma samples for determination of octreotide and serum samples for IGF-1 and GH levels were drawn pre-dose and over the 63-days post-dosing. Injection site reactions and AEs were recorded, scored and compared across groups. Results: MTD201 was very well tolerated by both groups with 3 mild TEAEs observed per group. Transient and mild injection site reactions were similar after all treatments. Upon MTD201 injection, a low initial burst of octreotide (<1ng/mL) was followed by a sustained period of release that extended beyond the final sampling point at Day 63. Cmax values of 5.42ng/mL (SC) and 3.68ng/mL (IM) were within the plasma exposure range reported for marketed octreotide products. Octreotide bioavailability was 47% (IM) and 62% (SC) relative to SIR. Sustained suppression of IGF-1 concentration was achieved throughout the study period to similar levels for both groups. Octreotide PK profiles and overall exposures were similar between groups, indicating that these routes may be interchangeable in clinical use.Conclusions: MTD201 (30mg) by either IM or SC injection produced continuous octreotide release over a period of at least 63 days at levels predicted to maintain efficacious plasma concentrations at steady state with a dosing interval of up to 8 weeks. Reduced plasma IGF-1 concentrations were maintained throughout the study period. Unlike marketed octreotide depot products, MTD201 can be simply and rapidly reconstituted in WFI to give a stable suspension injectable via 21G needle in a 1.5mL volume. MTD201 can be developed as an easy to inject SC or IM depot for acromegaly and NETs, with an expected dose interval of 8 weeks, and confirmed patient-centric advantages.
SUN-LB62 Differential Regulation of 22 kDa and 20 kDa Growth Hormone Isoforms in Response to Acute Glucose Load and Moderate Intensity Exercise
Authors: Haenelt Michael , Schilbach Katharina , Gar Christina , Longo Schweizer Junia Ribeiro de Oliveira , Nicolay Shiva Sophia , Andreas Lechner , Bidlingmaier Martin
Published: May 2020

Background: Among growth hormone (GH) isoforms, the 22kDa (22kD) is the most abundant (~90%), followed by 20 kDa GH ((20kD) ~10%). 22kD has known diabetogenic potential by increasing insulin resistance. Although of equal somatotropic activity, 20kD has been suggested to be less diabetogenic. Under physiological conditions, both isoforms are largely secreted in parallel, but data on regulation of both isoforms in the context of glucose load and utilization are scarce.

Methods: We measured 20- and 22kD GH in fasted healthy adult females during two scenarios: (A) Premenopausal females (n = 25; age (mean (range)) 27.8 (22-52), body mass index (BMI) (kg/m2) 21.8 (18.2-27.3), insulin sensitivity index (ISI) 7.9 (3.2-19.7) underwent an oral glucose tolerance test (OGTT, 75g, sampling at baseline, 30, 60, 90, 120 and 180 minutes (min); (B) Premenopausal females within 1 year postpartum (n=28, age 36 (29-44), BMI 23.7 (19.4-41.3), ISI (7.2- (2.4-13.2)) performed moderate intensity exercise (fixed workload 60% VO2max, sampling at -15, -10, -5, 0, 3, 6, 10, 15, 20, 30 and 45 min and after 5, 10 and 15 min of resting). 20- and 22kD were measured by specific immunoassays (22kD: IDS-iSYS GH CLIA, limit of quantification (LoQ) 0.05 ng/mL; 20kD: in-house immunofluorometric assay (IFMA), LoQ 0.025 ng/mL), and the 20/22kD ratio was calculated.

Results: As expected, both, 22kD and 20kD concentrations decreased after glucose load. However, the 20/22kD ratio increased significantly (Friedman test, P = 0.04, Kendall’s W 0.69, Conover’s post test: 0 vs. 60, 90 and 120 min; P = 0.018, 0.032 and 0.018, respectively. After 120 min, 20/22kD returned to baseline.

With exercise, both, 20- and 22kD increased. In contrast to glucose load, the 20/22kD ratio significantly decreased (Friedman test, P = 0.025, Kendall’s W 0.59, Conover’s post test: -10 vs. 10 and 20 min; P = 0.015 and 0.022, respectively), reaching a nadir at 10 min and returning to the baseline after cessation of exercise (20 vs. 50, 55 and 60 min; P = 0.02, 0.005 and 0.016, respectively.

Conclusion: Glucose load and exercise lead to opposite changes in the 20/22kD ratio, suggesting a tight regulation by glucose demands. We speculate that the putative less diabetogenic isoform (20kD) is preferentially secreted during situations of glucose excess, while the opposite happens during exercise, when increased energy demands are associated with predominant upregulation of the more diabetogenic 22kD GH.
SUN-933 Lactic Acidosis as a Rare and Unusual Presentation of Pheochromocytoma
Authors: Mohammad Nazar , Frith Margaret , Wilhelm Olayinka Olawale
Published: May 2020

Background: Pheochromocytoma is a rare catecholamine-producing tumor of chromaffin cells in the adrenal medulla or of a paraganglion. Typically it presents with sustained or paroxysmal hypertension, severe headaches, palpitations and sweating due to hormone excess. However, the presentation can be variable and can mimic many other diseases. If left undiagnosed or untreated, it can lead to life-threatening consequences.

Case Presentation:A 35 year old female with significant past medical history of migraine headaches, poorly controlled hypertension and a recent new onset seizure, presented with progressive worsening shortness of breath and persistent abdominal pain following a gastrointestinal illness. She also reported diaphoresis, cold fingers and toes, abnormal weight gain, and orthostatic symptoms that gradually worsened for two months prior to presentation. Laboratory evaluation revealed lactic acidosis, leukocytosis, and hypokalemia. Subsequently, a CT scan of the abdomen was performed that revealed an adrenal mass with significant elevation in urine metanephrines. As a result, the patient was diagnosed with pheochromocytoma and successfully treated with laparoscopic left adrenalectomy.

Conclusion: Pheochromocytoma is a rare but can be life threatening if left undiagnosed. It is of utmost importance for clinicians to keep in mind such unusual presentation of a potentially life threatening tumor. To the best of our knowledge, this is an unusual presentation of Pheochromocytoma with severe lactic acidosis.
SAT-LB90 Angiotensin II and ACTH Receptor Expression in Aldosterone-Producing Adenomas
Authors: Lim Jung Soo , Plaska Samuel , Rege Juilee , Turcu Adina F , Rainey William E
Published: May 2020

Background: The mechanisms leading to elevated aldosterone synthesis in aldosterone-producing adenomas (APAs) remain an area of active research. Aldosterone-driver somatic gene mutations that allow inappropriate intracellular calcium entrance have been identified in most APAs. Cell-based studies of such mutations indicate that responses to physiologic stimuli, such as angiotensin II or ACTH, are increased. Little is known, however, regarding possible variations in response to hormonal stimuli between APAs with different aldosterone-driver mutations. Herein, we analyzed the transcript expression of the ACTH receptor (MC2R), the melanocortin 2 receptor accessory protein (MRAP) and the type 1 angiotensin II receptor (AGTR1) in APAs with known aldosterone-driver somatic mutations. Methods: RNA was isolated from normal adrenal glands (n=8), and from APAs with mutations in: KCNJ5 (n=14), ATP1A1 (n=14), CACNA1D (n=14), and ATP2B3 (n=5). The gene expressions of MC2R, MRAP, AGTR1 and aldosterone synthase (CYP11B2) were quantified using qPCR and normalized to β-actin. Results: All APA mutation groups had significantly higher transcript levels of CYP11B2, MC2R and AGTR1 as compared to whole normal adrenals. While MRAP and AGTR1 transcripts were comparable between tumor mutation groups, MC2R expression was significantly lower in KCNJ5-mutated APAs compared to other APAs. Overall, CYP11B2 expression demonstrated positive correlations with MC2R (R=0.728, p<0.0001) and AGTR1 (R=0.397, p=0.006) in APAs. These correlations were strongest in APAs harboring ATP1A1 mutations, and weakest in KCNJ5-mutated APAs. Conversely, CYP11B2 did not correlate with MC2R and AGTR1 in the normal adrenals. Conclusions: ACTH and angiotensin II receptors are expressed in all APAs, regardless of the underlying aldosterone-driver somatic mutations. Further research to clarify the effects of ACTH and posture on aldosterone production from APAs could provide additional insight into developing diagnostic and subtyping tools for primary aldosteronism.
MON-LB305 The “Normal” Hormonal Levels in Athletes: Should Reference Ranges Be Adapted for the Physically Active Population?
Authors: Cadegiani Flavio , Abrao Tatiana P C , da Silva Pedro Luiz H , Kater Claudio E
Published: May 2020

Background:Despite the growing number of physically active subjects, including elite and amateur athletes, little is known regarding metabolic and hormonal chronic adaptations to exercises. While the elucidation of the hormonal and metabolic physiological adaptations to physical activity is of emerging importance, the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study have serendipitously unveiled the existence of multiple metabolic and endocrine physiological changes in male athletes, including chronic increase of testosterone with concurrent physiological increase of estradiol, enhanced GH and cortisol responses to stimulations,andincreased catecholamines, basal metabolic rate, fat oxidation, and hydration status. These findings were uncovered due to a novel methodological design in which athletes affected by overtraining syndrome (OTS) were compared to a two control groups, of healthy athletes (ATL) and healthy non-physically active controls (NPAC). Since none of the parameters were directly dependent on exercise or performance, differences between these two groups were unexpected. From the fact that several parameters were shown to be different between ATL and NPAC, we realized that the use of the reference ranges for general population to analyze results in athletes may potentially under- and over-diagnose a wide range of conditions. Our objective is therefore to determine whether athletes should be biochemically evaluated through specific adapted ranges, and propose preliminary adaptations in these ranges. Methods: A systematic review on the literature on endocrine and metabolic adaptations to exercise was performed, as well as a thorough analysis of the seven arms of the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study. Results:Multiple reference ranges were shown to be inaccurate for athletes. Among the parameters that should be adapted for athletes, and their respective adaptedranges include: 1. Cortisol response to an insulin stimulation test (ITT) (> 20.5 μg/dL); 2. GH response to an ITT (> 12 μg/L); 3. Prolactin response to an ITT (> 22 ng/mL); 4. Salivary cortisol at 8AM (> 450 ng/dL); 5. Total testosterone (> 450 ng/dL); 6. Estradiol (25-45 pg/mL) - and testosterone-to-estradiol ratio maintained > 13.7; 7. Total nocturnal urinary catecholamines (> 220 μg/12h); 8. Resting lactate (< 1.0 nMol/L); 9. Measured-to-predicted basal metabolic rate (BMR) (> 105%); 10. Fat oxidation (in relation to total BMR) (> 50%); and 11. Hydration status (body water > 62% of total body weight). Conclusion: Analysis of biochemical parameters in athleted should be interpreted with cautious, particularly hormonal and metabolic parameters, once many parameters likely undergo adaptive changes when under physical activity. Preliminary adaptations for the ranges have been proposed.
SAT-LB138 The LncRNA Growth Arrest Specific 5 Regulates Cell Survival via Distinct Structural Modules With Independent Functions
Authors: Frank Filipp , Kavousi Nadieh , Bountali Aikaterina , Dammer Eric , Mourtada-Maarabouni Mirna , Ortlund Eric
Published: May 2020

The growth arrest-specific 5 (gas5) gene encodes a long non-coding RNA (lncRNA) that is required for normal growth arrest, slows down the cell cycle, controls apoptosis, and is required for the inhibition of cell growth by mTOR inhibitors such as rapamycin. In agreement with this role in regulating cell proliferation, Gas5 expression is reduced and acts as a tumor suppressor in numerous cancers, including B-cell lymphoma and leukemia. At its 3’ terminal end (nucleotides 546-566) Gas5 contains a predicted stem-loop structure that specifically interacts with steroid receptors (SRs) and blocks DNA-dependent steroid signalling. In steroid-sensitive cancer cells such as prostate cancers this SR binding motif is responsible for Gas5 effects on cell growth. This is not true in other cell types, however, where proliferation is not strongly dependent on SR signaling (e.g. leukemic T cells). Therefore, other regions in Gas5 must be active and use different mechanisms to regulate cell survival. We have used SHAPE chemical probing to analyze the secondary structure of Gas5 in vitro and in cellulo. We find that the secondary structure of endogenous Gas5 resembles that of in vitro transcribed Gas5 RNA. The molecule contains three separate structural modules: a 5’ module with low secondary structure content, a highly structured core module, and the SR binding module, which forms separate from the rest of the molecule close to its 3’ end. Functional studies in leukemic T cells show that the 5’ module mediates Gas5’s role in inhibiting basal cell survival and slowing the cell cycle, whereas the core module is required for mediating the effects of mTOR inhibition. These results confirm that the Gas5 structural modules function independently in cells and each module acts under different cellular conditions, likely using different molecular mechanisms. RNA pull-downs from cell lysates using the identified modules and full-length RNA identified proteins preferentially associated with each module. Proteins preferentially associated with the 5’ terminal region are enriched in splicing and RNA processing factors. The structured central region preferentially interacts with proteins involved in chromosome organization such as the SWI/SNF family of nucleosome remodeling complexes.
SUN-LB64 Urine Phosphoethanolamine Is an Underutilized Biomarker for Hypophosphastasia
Authors: Shajani-Yi Zahra , Ayala-Lopex Nadia , Black Margo , Dahir Kathryn McCrystal
Published: May 2020

Hypophosphatasia (HPP) is a rare disease caused by a loss-of-function mutation in the ALPL gene leading to a deficiency in the tissue-non-specific isoenzyme alkaline phosphatase (ALP) and excess of extracellular inorganic pyrophosphate (PPi) and pyridoxal 5’phosphate (PLP). Patients with HPP have a widely variable clinical phenotype, from neonatal seizures and hypomineralization to isolated dental or joint disease in adults. Patients present with ALP activity levels below their age-adjusted reference interval and elevations in PLP. This variable clinical phenotype leads to significant diagnostic challenges, particularly in those with minor disease manifestations. Biomarkers for diagnosing HPP and monitoring patients on enzyme replacement therapy (ERT) are limited. Low ALP activity is not specific for HPP; it can be low in other conditions including untreated hypothyroidism, and other skeletal dysplasias. Accurate PLP assessment is limited in patients on ERT due to hydrolysis of the substrate. Phosphoethanolamine (PEA) is a substrate hydrolyzed by TNSALP and elevated levels of PEA may be observed in HPP, supporting the diagnosis of HPP, but have been reported to be non-specific. We hypothesized that urine PEA levels could be used to diagnose HPP and as a surrogate marker for ERT compliance. We performed a retrospective analysis on 83 adult patients (63F: 20M) presenting for investigation or follow-up of HPP from 7/1/2014 to 1/7/2020. Urine was sent to the Children’s Hospital in Colorado for PEA testing. Patients were diagnosed with HPP if they had ALP levels persistently below the age-adjusted reference interval, were positive for an ALPL gene mutation/had a family history of HPP and had musculoskeletal/dental symptoms consistent with the disease. Patients were negative for HPP if ALP was not persistently low, vitamin B6 levels were normal without supplementation, negative ALPL genetic testing results (when available) and no musculoskeletal/dental symptoms. PEA levels were not considered for diagnosis. The following was collected from the EMR: PEA results, diagnosis, and ERT status. PEA levels were higher in patients with HPP not on ERT (median=117.0, N=39) vs. those negative for HPP (median=24.0, N=15, p<0.0001). The receiver operator curve for PEA in diagnosing HPP had an AUC of 0.94 (SE=0.03, p<0.0001). Specificity was 100% at PEA levels >53.5 ng/ml (sensitivity=79.5%) with an NPV of 65.2% and PPV of 100%. Initial PEA values in patients with HPP and not on ERT were higher (median 117.0, N=39) than patients on ERT (median 65.0, N=16, p=0.004). Patients who began ERT had a decline in PEA levels after treatment (mean decrease 68.1%). PEA is a specific diagnostic marker for HPP in patients undergoing investigation for HPP and may be used as a surrogate marker to monitor ERT compliance. Future studies are necessary to evaluate the association between PEA levels and functional performance.