bluuebunny/crossref_metadata_2025 huggingface dataset:
MON-239 Pituitary Apoplexy Induced by Gonadotropin-Releasing Hormone Agonist Administration: A Rare Complication of Prostate Cancer Treatment
Authors: Barbosa Mariana Marques , Paredes Sílvia Cristina de Sousa , Machado Maria João , Almeida Rui , Marques Olinda Castro
Published: May 2020

Background: Pituitary apoplexy is a potentially life-threatening clinical condition associated with bleeding and/or infarction into the pituitary gland, usually within a tumor. Gonadotropin-releasing hormone (GnRH) agonists, currently used in the treatment of advanced prostate cancer, have been described in the literature as a rare cause of pituitary apoplexy.

Case: We report the case of a 69 year-old man with a known pituitary macroadenoma incidentally detected in 2016, without further investigation. He was diagnosed with prostate cancer in 2017 and underwent retropubic prostatectomy. Two years later there was evidence of histologic prostate tumor progression, so he started treatment with leuprorelin 45mg (GnRH agonist). Immediately after the first subcutaneous injection he presented with acute-onset severe headache, followed by left eye ptosis, diplopia and vomiting. Left cranial nerve III palsy was confirmed by examination in the emergency department. Head computed tomography showed a lesion in the sellar region; laboratory endocrine workup was significant for total testosterone 72.07 ng/dL (86.49 – 788.22), with no other abnormalities. Magnetic resonance imaging of the pituitary revealed tumor enlargement and a T1-hyperintense signal, compatible with recent haemorrhagic sellar content. The patient was managed conservatively with high dose steroids, and symptoms were significantly improved on discharge.

Discussion: Pituitary apoplexy induced by GnRH agonist administration is a rare complication, described in only 20 documented cases to date. The pathophysiologic mechanism involved is not clearly established and several hypotheses have been proposed: a combination of metabolic hyperactivity, cell division/tumor growth and increased intrasellar pressure, inducing ischemia in a poorly perfused adenomatous tissue given the demand. Although uncommon, healthcare professionals should be aware of this serious consequence of GnRH agonist administration and recognize the signs, preventing a delay in diagnosis and treatment.
SUN-044 Gonadotropin Releasing Hormone (GnRH) Agonist Therapy Induces a Sustained Reduction in Plasma Testosterone Levels and Is Well Tolerated in Transwomen Veterans
Authors: Gondin Lyan , Trejo Jonathan , Pinkson Sheila , chen xi , Case Emina , Wortham Joy , koops Maureen , Tripathy Devjit
Published: May 2020

Gender affirming hormone therapy (GAHT) is the mainstay of long-term management of transgender individuals. In transwomen, treatment with physiologic doses of estrogen alone is often insufficient to suppress testosterone to the desired level. Although GnRH agonist therapy is usually prescribed for puberty suppression in trans youth, in adult transwomen, GnRH agonist may be added. The durability of long-term GnRH agonist in lowering testosterone as well as the long-term safety is not clear. We examined the effect of leuprolide a GnRH agonist, on testosterone as well as clinical and metabolic features in transwomen Veterans. Out of 91 subjects with gender dysphoria followed at a VA Endocrinology clinic, 65 were transwomen (age 49 ± 3 years) who had a detailed clinical, biochemical and hormonal profile (lipid profile, HbA1C, FPG, testosterone, estradiol). We performed a retrospective cohort study of the 31 (48%) transwomen on Leuprolide (3.375mg q month) and 33 transwomen who were not on Leuprolide. Plasma testosterone, lipid profile, were analyzed before, 6 months, 1 year and at the last follow-up visit. The median follow-up of subjects on Leuprolide was 2.7 (1.7-3.8) years. Plasma testosterone concentration declined by 89% from 432±32 ng/dl to 47±9 ng/dl within 3-6 months after initiation of GnRH agonist treatment. Plasma testosterone remained persistently low 39±4ng/dl at 1 year and at the end of 2.7 yrs, most subjects on Leurprolide had plasma testosterone concentration <50ng/dl. Leuprolide therapy led to similar rapid decline in testosterone concentration in both younger (<40yrs) or relatively older (>50yr) transwomen. Leuprolide was in general well tolerated requiring discontinuation in just one patient due to severe fatigue. Three subjects (10%) experienced hot flashes which did not lead to discontinuation of medication. In the non-Leuprolide group, of 33 subjects, the follow-up was relatively inconsistent and only 12 subjects were regularly followed throughout a year with stable treatment. The decline in plasma testosterone was of a lower magnitude versus the leuprolide group (55% vs 89%, p <0.05). The testosterone levels declined from 393±42 to 180±44 ng/dl at 6 months. Body weight, and lipid profile: triglyceride, and plasma HDL concentration did not change significantly with or without GnRH agonist therapy. In conclusion, GnRH agonist therapy led to a sustained suppression of plasma testosterone levels in transwomen and was not associated with worsening lipid profile, was effective, and well tolerated in transwomen regardless of their age and may be considered an adjunct to the ant-androgen and estrogen therapy.
SUN-140 TMEPAI Inhibits SMAD 2/3 Mediated Muscle Wasting
Authors: Kharoud Swati , Walton Kelly Louise , Hagg Adam , Goodchild Georgia , Chen Justin , Thomson Rachel , Qian Hongwei , Gregorevic Paul , Harrison Craig Anthony
Published: May 2020

Inhibition of myostatin and activin activity using ligand traps, such as soluble receptors, follistatin and propeptides, can markedly increase skeletal muscle mass in healthy mice and ameliorate wasting in models of cancer cachexia and muscular dystrophy. Though effective, clinical translation of these approaches has been hindered by off-target effects. Toward the goal of developing tissue-specific myostatin/activin interventions, we explored the ability of transmembrane prostate androgen-induced (TMEPAI) to promote growth of skeletal muscle. TMEPAI, a transcriptional target of activin in muscle, is a known inhibitor of TGF-β1-mediated SMAD 2/3 signalling. In this study we show that TMEPAI also blocks activin A, activin B, myostatin and GDF-11 in vitro activity. Adeno-associated viral (AAV) gene delivery of TMEPAI into healthy mice increased local muscle mass by as much as 30%. Increased muscle mass was attributed to hypertrophy of fibres in TMEPAI-expressing muscles, and was coincident with an upregulation in markers of protein synthesis (pAkt, pMTOR, p70S6K). The ability of TMEPAI to block activation of the canonical activin/myostatin-SMAD 2/3 axis, was demonstrated by co-injecting AAV6:activin A and AAV6:TMEPAI into healthy mice. In this setting, TMEPAI blocked activin-induced phosphorylation of SMAD3 and associated skeletal muscle wasting. Finally, delivery of AAV6:TMEPAI into tibialis anterior muscles of mice bearing C26 tumours prevented muscle atrophy normally associated with this model. The results support that viral gene delivery of TMEPAI can effectively increase muscle mass via inactivation of the activin/myostatin-SMAD 2/3 pathway.
SAT-631 Increased Incidence of Diabetic Nephropathy in Veterans with Severe Insulin Resistance
Authors: Trejo Jonathan , Hernandez Lyan Gondin , Esteve Lucy M A , Vasquez Libia , Pinkson Sheila , Chen Xi , Koops Maureen , Tripathy Devjit
Published: May 2020

Recently, cluster analysis has been used to classify adult onset diabetes based on pathophysiologic profile. Using autoimmunity status, BMI, insulin resistance, and beta cell function, this classification system can predict diabetes associated complications. Individuals with primarily insulin resistant phenotype have been associated with increased incidence of nephropathy while those with insulin deficient phenotype are associated with retinopathy. Clinically, patients with severe insulin resistance can be defined as those who require high doses of insulin to achieve glycemic control, such as patients on U-500 insulin requiring more than 200 units of insulin a day. To characterize the clinical and metabolic phenotype of insulin-resistant patients from a South Texas VA diabetes clinic, we evaluated presence of macro or microvascular complications and beta-cell autoimmunity and function in this population. A retrospective cohort study was completed at the South Texas VA Diabetes Clinic. Charts were reviewed for anthropometric measurements, presence of macro and microvascular complications, anti-diabetic medication, lipid profile and HbA1c over 3 visits, autoimmunity (anti-GADab), and beta-cell function (fasting C-peptide). Patients with insulin doses >200 U/day or on U-500 insulin were categorized as “severe insulin-resistant”. Those with insulin doses < 0.5 U/kg/day were categorized as “mild insulin resistance” as a control group. Out of 120 patients, 30 met criteria for severe insulin resistance (n=30, M/F=29/1 age 61±1.6 years (yr), BMI 41±0.9 kg/m2, duration of diabetes 18.3±0.3 yr, HbA1c -8.4±0.2%, total daily insulin dose (TDD) 301±31U). 30 patients with insulin use <0.5 U/kg/day met criteria for mild insulin resistance (N=30, M/F: 28/2, age 62±2 yr, BMI 30±1 kg/m2, duration of diabetes 12±1.2 yr, HbA1c 7.2±0.2%, TDD 17±2U). Prevalence of nephropathy was higher in the insulin resistant group vs the mild insulin resistant group (76% vs 43%, p<0.05). There was no difference in prevalence of retinopathy (p=0.095) or CAD (p=0.6) between the groups. There was no difference in use of ACE-i or SGLT-2i between the groups. Insulin resistant subjects had a higher plasma triglyceride (325±0.3 vs 202±0.3 mg/dl, p=0.04). Prevalence of GAD ab was not different between the groups (3% vs 0%). Fasting C-peptide concentrations were similar in both groups (5.6±0.3 vs 5.2±0.25 ng/ml, p=0.3). HbA1c in the insulin resistant group improved between visits 1 and 3 (p<0.01). Weight increased over three visits in the severe insulin resistant group as opposed to mild weight loss in the mild insulin resistant group.

Our results support the high prevalence of diabetic nephropathy in patients with severe insulin resistance, although it is unclear that insulin resistance is the etiology. Long-term follow up of these patients may provide insight into the underlying mechanisms of these complications.
SUN-015 Developmental Programming: Depot-Specific Inflammatory State and Distribution of Thermogenic Adipocytes Programmed by Gestational Testosterone Excess
Authors: Ciarelli Joseph Norman , Puttabyatappa Muraly , Padmanabhan Vasantha
Published: May 2020

Prenatal testosterone excess induces insulin resistance, dyslipidemia and cardiovascular defects in ewes. Considering adipose depots influence systemic metabolic status, disruptions in visceral (VAT), subcutaneous (SAT), pericardiac (PCAT) and perirenal (PRAT) adipose depots may contribute to these metabolic defects. While the changes in PCAT and PRAT in the prenatal T-treated sheep are unknown, we found an increase in the oxidative stress and inflammatory state in the VAT but not SAT, while insulin sensitivity is maintained in both depots (Biol Reprod 2016;94:113). Although all four depots are rich in white adipocytes that specialize in lipid storage, it is not clear what underlies the depot-specific differences. A potential contributor may relate to depot-specific differences in presence of brown/beige adipocytes. Brown/beige unlike white adipocytes are thermogenically active due to their expression of uncoupled protein 1 (UCP1), which uncouples mitochondrial oxidative phosphorylation to release stored energy as heat. Because they favor lipid utilization rather than storage they promote a metabolically healthy phenotype. We hypothesized that the relative distribution of brown/beige adipocytes may contribute to the depot-specific changes in inflammatory state. To test this, adipose depots from control (n=6) and prenatal T- (100mg T propionate twice a week from days 30-90 of gestation)-treated (n=5) female sheep were studied at 21 months of age. The changes in expression of inflammatory and thermogenic adipocyte markers were assessed by real time RT-PCR and data analyzed by Student’s t-test and Cohen’s effect size analysis. Prenatal T-treatment induced 1) significant increase in inflammatory cytokine interleukin 6 in VAT and PRAT while decreasing it in PCAT 2) significant increase in tumor necrosis factor in the VAT and a trend (evident by effect size analysis only) for an increase in SAT and PCAT and 3) significant increase in PRAT and a trend toward increase in the macrophage marker CD68 expression in VAT. Among the thermogenic gene markers, the expression of UCP1 was significantly increased in VAT and PCAT with a trend for an increase in PRAT. The expression of UCP2 and PPAR gamma co-activator 1 beta (PPARGC1B) were also significantly elevated in VAT with a trend for an increase in SAT. These findings are indicative of depot-specific differences in prenatal T-induced inflammatory status with effects being pronounced in VAT compared to other depots. The increases in thermogenic markers in adipose depots do not support our hypothesis but rather are reflective of a compensatory response to promote adipose depot insulin sensitivity and may have a bearing on function of organs in the proximity of respective depots. These findings are likely of translational significance in metabolic disorders associated with hyperandrogenic state.
OR14-02 Circadian Regulation of Chromatin State Mediates Pancreatic Islet Incretin Response
Authors: Weidemann Benjamin John , Kobayashi Mikoto Alfred , Marcheva Biliana , Bass Joseph T
Published: May 2020

The circadian clock is programmed by an autoregulatory transcription feedback loop present in brain and peripheral tissues that coordinates metabolism with nutritional state and the sleep-wake cycle. Epidemiologic and genetic studies indicate circadian disruption as a risk factor in the development of diabetes. We have demonstrated that conditional ablation of the β cell clock in adult life leads to hypoinsulinemic diabetes, and through mRNA-sequencing in mouse and human islets we revealed clock control of gene networks involved in insulin secretion, nutrient sensing, and exocytosis. A remaining question is: How does the core molecular clock modulate time-of-day dependent chromatin state to regulate pancreatic islet response to glucose and insulin secretagogues? Here we report that loss of the pancreatic β cell molecular clock results in closed chromatin at cAMP-responsive gene regulatory elements and dysregulated cAMP-dependent coregulator recruitment following cAMP agonism, consistent with a role for the molecular clock in mediating cell response to environmental stimuli. Further, tandem analyses of ATAC- and ChIP-sequencing in synchronized islets revealed dynamic chromatin accessibility across the 24-hour cycle at genes regulating insulin secretion and at genomic regions enriched for signal-inducible and circadian transcription factor motifs. Our genome-wide sequencing reveals a new role for the clock in global chromatin remodeling underlying the incretin response in pancreatic β cells.
MON-016 Neural Circuits and Hormonal Mechanisms Underlying the Negative Impact of Stress on Pregnancy Outcomes
Authors: Gotlieb Neta , Wilsterman Kathryn E , Finn Samantha L , Browne Madison , Hu Damhee , Cornejo Diana , Hutchinson Gwyneth , Iwakoshi-Ukena Eiko , Ukena Kazuyoshi , Bentley George E , Kriegsfeld Lance J
Published: May 2020

Despite numerous findings detailing the negative impact of stress on female reproductive health, the means by which stress acts on the CNS and periphery to compromise reproductive success remains poorly understood. As a result, the current study sought to clarify the neuroendocrine mechanisms by which stress acts on the brain to deleteriously influence pregnancy outcomes. Reproduction is regulated by the hypothalamo-pituitary-gonadal (HPG) axis, with hypothalamic gonadotropin-releasing hormone (GnRH) neurons representing the final, common pathway of this axis. Cells expressing the inhibitory neuropeptide, RFamide-related peptide-3 (RFRP-3), lie upstream of the GnRH system and are markedly regulated by environmental and psychosocial factors, including stress. In the present study, we asked whether RFRP-3 neurons mediate the effects of stress on pregnancy outcomes through the regulation of prolactin secretion, as prolactin is critical for pregnancy maintenance. More specifically, because specialized hypothalamic dopaminergic neurons, namely tubero-infundibular dopaminergic (TIDA) neurons, are major regulators of prolactin secretion, we hypothesized that RFRP-3 neurons directly target TIDA cells to negatively influence fetal development. To test this possibility, we subjected pregnant mice to chronic restraint stress for the first half of pregnancy and performed a broad screen of hypothalamic neuroendocrine function compared to non-stressed controls. Stressed mice exhibited elevated baseline concentrations of corticosterone that remained high at least 6 days after the final exposure to stress. Whereas progesterone concentrations were reduced by stress early in pregnancy, stressed mice recovered typical progesterone secretion during late gestation. These early, stressful experiences resulted in persistent developmental delays, reduced embryo weight, and abnormal placental histology. Significantly, a small percentage of TIDA cells receive close contacts from RFRP-3 axons, providing a mechanism for the control of prolactin secretion by stress. However, contrary to expectation, the percentage of TIDA neurons receiving input from RFRP-3 cells was not impacted by stress. Together, these findings identify a potential pathway of control for the impact of stress on neuroendocrine factors critical to pregnancy success, although further work using more sensitive approaches is needed to examine the putative role of RFRP-3 on stress-induced pregnancy outcomes.
MON-510 Patients with Large Multinodular Goiters Operated for Presumed Benign - Large or Growing Thyroid Nodules, Have a High Likelihood of Significant Synchronous Thyroid Cancers
Authors: Bantouna Dimitra , Paparodis Rodis , Karvounis Evangelos , Livadas Sarantis , Chourpiliadis Charilaos Paulos , Hourpiliadi Hara , Shanawaz Imam , Jaume Juan Carlos
Published: May 2020

Introduction: Despite the current state of evidence suggesting that thyroid nodules’ size should not be the sole criterion for the decision to undergo thyroidectomy, many patients are still operated for large, or growing nodules. In order to ascertain whether this is a justifiable approach, we performed the present study.

Methods/ Subjects: We reviewed the data from two prospectively collected databases of patients undergoing thyroid surgery in two tertiary referral centers, one in the USA (A) and the other one in Greece (B) over 14 consecutive years. We collected data on the preoperative surgical indication, FNA cytology and surgical pathology. We included subjects with multinodular goiters, operated solely for large or growing thyroid nodules, who did not have any known or presumed thyroid cancer, or indications of high risk for malignancy (FNA suspicious for thyroid cancer, follicular neoplasm, suspicious for follicular neoplasm, FLUS/AUS, cellular specimen), family history of thyroid cancer or prior neck radiation exposure.

Results: We reviewed 5523 consecutive cases of thyroid surgery (A:2711, B:2812). After excluding n=3059 subjects, we included n=2464 subjects in the present analysis. Overall 535 thyroid cancers were identified (21.7%): 349 (65.2%) were microcarcinomas (<1cm), 161 (30.0%) were macrocarcinomas (≥1cm) and 25 of undetermined size. The histology was consistent with papillary cancer (PTC) n=500, follicular cancer (FTC) n=14, Hurthle cell cancer (HCC) n=9, medullary cancer (MTC) n=4, thyroid lymphoma n=1 and mixed histology cancers n=4. In n=68 (2.75%) cases, a thyroid cancer was found in the large or growing thyroid nodule, which was the original indication for surgery. The cancers were multifocal in n=165 subjects; there was extrathyroidal extension in n=61, capsular invasion was present in n=80, lymph node involvement in n=35 and bone metastasis in n=2 subjects.

Conclusions: Although the likelihood of identifying a clinically relevant thyroid cancer in a large or growing nodule, in the absence of risk enhancing features, is low; the risk of synchronous, clinically important, thyroid cancers is high in patients with large multinodular goiters. Therefore, more precise screening strategies are urgently needed to identify the patients, who would clearly benefit from thyroid surgery and protect those who do not need to be operated on.
SAT-718 Inhibition of Androgen Receptor Activity by DDE Is Affected by Mutations in the BF3 Site
Authors: Lozano Andrea , Kotsikorou Evangelia , Dean Frank B
Published: May 2020

The androgen receptor (AR) plays an important role in the development of the male phenotype and traits. Some diphenyl compounds inhibit AR activity by binding to a hydrophobic surface binding site, BF3. A similar diphenyl structure is found in 4,4’ DDT and its breakdown product 4,4’ DDE. Previous results showed that DDT and DDE induced the release of bound dihydrotestosterone from the AR ligand binding domain, with IC50 values ranging from 54 to 82uM. This suggested that DDT and related compounds may act as endocrine disrupting chemicals by binding to the BF3 site and inducing allosteric changes in the AR structure, disrupting binding of the steroid to the ligand binding domain. Here, an AR reporter system was transiently transfected into HEK293 cells and AR activity was measured using a dual luciferase assay. The system was used to measure the response of the AR protein to varying concentrations of dihydrotestosterone in the presence and absence of DDE. DDE inhibited the activation of AR by dihydrotestosterone under these conditions. Five mutant AR genes with amino acid changes in the BF3 site were tested for alterations in the ability of DDE to disrupt AR activity. The five mutations tested were F673K, F673W, G724R, G724M, and L830D. The ability of DDE to inhibit AR activity was reduced by the mutations in the BF3 site. These results suggest that DDE acts as an endocrine disrupting chemical (EDC) by binding to the BF3 site and allosterically regulating AR activity.
MON-445 A Rare and Unusual Presentation of Adenoid Cystic Carcinoma as Thyroid Mass with Metastasis to the Lung
Authors: Maita Yousef , Osman Fawsia , Ewongwo Agnes , Zabad Manal , Horani Mohamad Hosam
Published: May 2020

Introduction: Adenoid cystic carcinoma is a rare form of cancer that most commonly originates within the secretory cells of the major and minor salivary glands. In rare and unusual cases, adenoid cystic carcinoma can present as Thyroid mass. Adenoid cystic carcinoma is described presenting in papillary carcinoma of thyroid and as poorly differentiated thyroid carcinoma with mixed or unclear histology. We describe the case of a patient diagnosed with poorly differentiated thyroid carcinoma with complete thyroidectomy later presenting with metastatic lung disease diagnosed as adenoid cystic carcinoma.

Case Presentation: A 53-year-old male with history of palpable neck mass, lymphadenopathy, and hoarseness with a diagnosis of poorly differentiated thyroid carcinoma with unclear histology. He underwent total thyroidectomy with level 6 compartment neck dissection, laryngeal nerve sparing with tracheostomy tube. Patient presented 2 months’ post thyroidectomy with right facial swelling. Labs were significant for microcytic anemia with Hgb 10, MCV 71, TSH and metabolic panel within normal limits. Radiographic imaging demonstrated residual-recurrent malignancy in the thyroid bed, lymphatic disease, and compression of surrounding structures including trachea, distal right internal jugular, and right subclavian vein. Follow up radiographic studies showed a 1.7 x 4.6 x 5.5cm soft tissue mass behind the trachea at the level of previously resected mass. Multiple pulmonary nodules were noted. Image guided needle biopsy of largest left lung nodules carcinoma with adenoid cystic pattern. Final path report was metastatic adenoid cystic carcinoma.

Conclusion: This case is unique in that it describes a rare and uncommon presentation of adenoid cystic carcinoma as metastatic thyroid carcinoma in a patient with prior history of thyroidectomy. Adenoid cystic carcinoma is a rare glandular malignancy that commonly presents as the second most common histologic subtype of salivary cancer. Adenoid cystic carcinoma as a histologic subtype has a high morbidity and mortality, if not identified and managed promptly. Prognosis and survival outcomes are poor with some studies comparing its prognosis to that of anaplastic carcinoma. This case also illustrates the complexity and diverse presentation of adenoid cystic carcinoma. The initial diagnosis in this patient was nonspecific with biopsy revealing poorly differentiated carcinoma. Adenoid cystic carcinoma was diagnosed later at time of disease progression to the lung. This case reviews the diagnostic workup, evaluation, and appropriate management of adenoid cystic primary thyroid carcinoma. In addition, it evaluates the appropriate differential diagnosis in patients enlarging neck mass and progressive thyroid cancer.
MON-135 Improving Thyroid Fine Needle Aspiration Education: Implementation of a Formal Clinical Procedure Assessment Tool for Teaching Thyroid FNA to Endocrinology Fellows
Authors: Jaisinghani Priya , Cohen David A , Lubitz Sara E
Published: May 2020

Fellows must demonstrate competence in the performance of thyroid biopsy (bx) from the 2019 ACGME Program Requirements for GME in Endocrinology, Diabetes, and Metabolism. During fellowship, trainees are often taught thyroid bx using an unstructured approach, through demonstration followed by supervised performance on patients. Concerns regarding patient safety, lack of readily available faculty & patients, and lack of competency checkpoints limit the utility of such an approach to teaching procedural skills (1). Application of Psychomotor Learning Theory to teaching procedural skills has modified prior philosophy to “learn, see, practice, prove, do, maintain.”  (2) Two phases exist: 1) cognitive- conceptualization and visualization of the procedure and 2) psychomotor- acquisition of procedural skills. Formal training has been shown to improve FNA diagnostic accuracy along with fewer surgical procedures for benign lesions.(2) There is no evidence to support any specific recommendations for training fellows on safe and efficient thyroid bx techniques further highlighting the need for a competency based approach.(3) Since the didactic lecture format is not well suited for the acquisition of complex manual operations, in our study, we seek to 1) create, implement, and standardize the thyroid FNA curriculum for Endocrine fellows at our institution by employing global learning objectives and a skill checklist to help guide competency, and 2) assess the impact of this curriculum on knowledge, performance, and comfort. The goal is to prepare fellows for unsupervised practice through clinical procedure assessment tools to guide practical learning in conjunction with didactic lectures. Curriculum could be implemented not only across the nation to other endocrine fellowships but widely across multiple disciplines such as otolarynology, radiology, pathology. To assess the nationwide need for a formal means of teaching and evaluating thyroid US/ FNA skills within fellowship programs, we will be administering a nationwide survey to all Endocrinology Program Directors and recently graduated Endocrinology Fellows.

1.Vogelgesang, S. A., Karplus, T. M., Kreiter, C. D. (2002). An instructional program to facilitate teaching joint/soft-tissue injection and aspiration. Journal of general internal medicine, 17(6), 441–445.

2. Ljung, B., Drejet, A., Chiampi, N., Jeffrey, J., Goodson, W. H., Chew, K, Miller, T. R. (2001). Diagnostic accuracy of fine-needle aspiration biopsy is determined by physician training in sampling technique. Cancer, 93(4), 263-268. doi:10.1002/cncr.9040.

3. Pitman, B., Abele, J., Ali, S. Z., Elsheikh, T. M., Jeffrey, R. B., Scoutt, L. (2008). Techniques for thyroid FNA: A synopsis of the National Cancer Institute Thyroid Fine-Needle Aspiration State of the Science Conference. Diagnostic Cytopathology Diagn. Cytopathol., 36(6), 407-424. doi:10.1002/dc.20829.
SUN-499 Extragonadal Germ Cell Tumor Induced Thyrotoxicosis
Authors: Diedrich Veronica , Foster Jennifer , Leonard Talayna , Shahlapour Mahmood , Horani Mohamad Hosam
Published: May 2020

Background: Extragonadal Germ Cell Tumors (EGCTs) are extremely rare, with an incidence of around 1/1,000,000 and highly variable prognosis dependent on subclassification as seminomatous or non-seminomatous. Non-seminomatous germ cell tumors can cause significant enough elevations in hCG to induce thyrotoxicosis via structural homology allowing for cross-reactivity with the TSH-receptor. Limited cases involving EGCTs inducing thyrotoxicosis have been studied.

Case: A 27-year-old male presented to the emergency department with intractable abdominal and back pain. He reported night sweats, nausea, dizziness, and a 10 lb weight loss in 1 week. He was resting comfortably and only complaining of pain. He was moderately tachycardic, tachypneic and hypertensive, with a physical exam only remarkable for tenderness to palpation of the abdomen. Abdominal CT revealed mesenteric and retroperitoneal lymphadenopathy, bilateral adrenal enlargement, a mass in the head of the pancreas, as well as gallbladder and common bile duct distention. Lymph node biopsy was conducted for a suspected lymphoma; however, pathology found a poorly differentiated carcinoma. A diagnosis of a non-seminomatous EGCT was made when ultrasound of the testes was negative for masses and labs revealed elevations in hCG (74842 mIU/ml), and LDH (1421 U/L) with normal AFP (6.98 ng/mL). Further workup showed a slightly elevated T4 Free Thyroxine (1.55 ng/dl) with normal TSH (0.555 mIU/L); thus his thyrotoxicosis was secondary to the high HCG. Treatment for thyrotoxicosis was deferred with the expectation that symptoms would resolve when the tumor burden was decreased. Our patient had numerous other complications requiring management from nephrology, GI and urology teams in addition to endocrinology and hematology-oncology. Bleomycin, Etoposide and Cisplatin (BEP) combination chemotherapy was initiated after recovery from acute complications. Further pathology evaluation suggested tumor susceptibility to the biologics nivolumab and pembrolizumab.

Conclusion: Patients with thyrotoxicosis secondary to metastatic non-seminomatous germ cell tumors often present with widespread metastasis and relatively few symptoms of thyrotoxicosis that resolve as the hCG levels decrease with chemotherapy without specific antithyroid medication. This case highlights the importance of considering clinically occult thyrotoxicosis in patients who have elevated hCG secondary to germ cell tumors. Early detection of germ cell tumor and recurrence is crucial for chemotherapeutic success. Thus, patients should be closely followed for thyrotoxicosis relapse which could potentially herald a carcinoma relapse and aid in early diagnosis.
SAT-550 Changes in Albuminuria Precede Dietary Sodium-Dependent Changes in BP During Aging - a Longitudinal Study
Authors: Katayama Isis Akemi , Nascimento Mariana M , Cullinane Danielle , Oliveira Ivone B , Williams Gordon H , Heimann Joel C , Pojoga Luminita
Published: May 2020

Background: Hypertension (HT) is a well-established independent risk factor for adverse cardiovascular and renal (CVR) outcomes and a high salt (HS) diet is the main cause for high blood pressure (BP). Despite extensive research focusing on HT, surprisingly there are no longitudinal studies assessing the long-term effects of HS. Aims: This study aimed (1) to evaluate the timing of onset for changes in CVR health during long-term sodium loading and (2) to assess whether salt restriction can prevent these effects.

Methods: C57BL/6 mice were randomized to HS, moderate (NS) or low (LS) salt diet and followed longitudinally for 50 weeks (wks). BP, urinary albumin/creatinine ratio (AC), plasma aldosterone (PA) and renin activity (PRA) were assessed monthly. At the end of the study, renal artery resistance and left ventricular (LV) parameters were measured by ultrasound and echocardiogram. Renal AT1 expression (Western Blot) and activity (IHQ) were quantified.

Results: At the beginning of the study, there were no differences in BP and AC between the three dietary groups. Relative to wk 1, BP (mmHg) in the HS group was higher in wk 21 (131±1.7 vs. 115±3.0, p= 0.05). Sodium restriction delayed this increase: SBP was higher in wk 41 in the NS group compared to the wk 1 (128±3.4 vs. 115±6.4, p= 0.05) but did not reach significance in the LS group until the end of the study. Similarly, relative to wk 1, AC (µg/mg) only in the HS group reached significantly higher levels in wk 17 (44±4.2, p<0.05). Again, sodium restriction delayed the occurrence of renal damage. AC reached significance in wks 25 and 41 for NS and LS (35±1.1 and 42±2.6 respectively, p<0.05 vs. baseline). Interestingly, the changes in AC always preceded the changes in BP, irrespective of diet. PA and PRA were appropriately activated by dietary salt restriction and suppressed by aging. The aging-induced suppression appeared stronger for PA than for PRA in the HS group only. Long-term sodium loading (HS) induced increased renal resistance, which was prevented in the LS but not in the NS group. Relative to HS, the LV mass index and cardiac output were lower in the NS and LS groups (p<0.05). LV volume indices and ejection fraction did not differ between groups. Renal AT1 protein expression and activation status (IHQ) were decreased in the sodium restricted group. Conclusions: Our study showed that long-term exposure to HS induced a progressive increase in BP and AC in mice. Importantly, these changes were delayed by long-term reduction in sodium intake. Interestingly, changes in AC preceded those in BP, irrespective of diet. Cardiac parameters suggest a sodium-induced eccentric cardiac hypertrophy in the older age, which was prevented by sodium restriction. One possible mechanism behind these effects is the overactivation of the AT1 receptor pathway.
SAT-250 A Case of Late Recurrent Cushing’s Disease Presenting with Proximal Myopathy
Authors: Barsamyan Gayane , Roper Steven N , Lobo Brian C , Woodmansee Whitney W
Published: May 2020

Patients with Cushing’s disease (CD) present with a variety of symptoms and comorbidities including central obesity, hypertension, hyperglycemia, fatigue, weakness, insomnia and mood changes. Proximal myopathy is one of the classical signs of hypercortisolism and patients typically report difficulty rising from a seated position or climbing stairs. Due to variability in clinical presentation, with some patients showing subtle or few symptoms, the diagnosis of CD can be delayed. We describe a patient with late recurrent CD whose primary symptom was proximal myopathy. A 63 yr. old man presented to our clinic with complaints of progressive muscle weakness and fatigue. He had been successfully treated for CD at age 35 with transsphenoidal pituitary adenomectomy. He had been on hormonal replacement therapy for panhypopituitarism since surgery including levothyroxine, testosterone and glucocorticoids. He noted progressive weakness for several years prior to presentation in our clinic. Earlier evaluations revealed vitamin B12 and vitamin D deficiency, but supplementation did not lead to significant symptom improvement. He suffered two episodes of unprovoked deep venous thrombosis with pulmonary embolism and developed a left biceps tear that required hospital admission. During admission, his muscle weakness was exacerbated by immobility and he was subsequently referred to endocrinology for consideration of steroid induced myopathy. He had been on physiologic glucocorticoid replacement since diagnosed with panhypopituitarism. At the time of our evaluation, he was able to ambulate with a walker, but was unable to climb stairs, drive a car and required assistance with activities of daily living. His only other symptoms were fatigue and insomnia. Laboratory testing after holding prednisone revealed: morning cortisol 31.7 mcg/dl (reference interval [RI], 4.0-22.0), ACTH 128 pg/mL (RI 6 - 50), FSH <0.7 mIU/mL (RI 1.6 - 8.0), LH <0.2 mIU/mL (RI 1.6 - 15.2), testosterone 85 ng/dL (RI 250 - 827), IGF-1 55 ng/mL (RI 41 - 279), prolactin 4.9 ng/mL (RI 2.0 - 18.0), TSH 0.01 mIU/L (RI 0.40 - 4.50), free T4 1.5 ng/dL (RI 0.8 - 1.8), HbA1c 6.8% (RI <5.7%). Prednisone was discontinued and hypercortisolism was confirmed by 1 mg overnight dexamethasone (dex) suppression test (Cortisol 32.4 mcg/dL, dex 517 ng/dL, RI 180-550 ng/dL) and elevated 24 h urine free cortisol 315.4 mcg/24h (RI 4.0 - 50.0). 8 mg DST showed mild cortisol suppression (Cortisol 21.2 mcg/dL, dex >1000 ng/dl). MRI confirmed recurrent tumor (1.2 x 0.8 x 1.3 cm) extending into the right cavernous sinus and the patient underwent repeat transsphenoidal tumor resection. Pathology confirmed ACTH adenoma. Our case report highlights that patients with CD can have late recurrences and require long term monitoring for return of hypercortisolism, even in cases of prior panhypopituitarism.
MON-328 Disorders of Glucose Metabolism in Cushing Syndrome in Uzbekistan
Authors: Narimova Gulchekhra Djumaniyazovna , Khalimova Zamira Yusufovna , Narimova Malika Ikramovna
Published: May 2020

Relevance. Cushing’s Syndrome (CS) is a serious risk factor for developing impaired glucose tolerance disorder (GTD) and a manifestation of secondary diabetes mellitus (DM). On the other hand, the development of impaired glucose metabolism affects not only the course but also the outcome of SC. Moreover, their frequency varies from 10% to 45% of all cases of SC. The aim of investigation - to evaluate the frequency of various forms of impaired glucose metabolism in patients with SC according to the national registry in the Republic of Uzbekistan. Materials and methods. The object of the study was 264 patients included in the register, 182 women (68.9%); men 82 (31.1%) aged 16 to 49 years. Including ACTH dependent CS (ACTH-DS) 219 (82.9%), ACTH independent CS (ACTH-IS) 41 (15.5%), ACTH ectopic CS (ACTH-ES) 4 (1.5%). The levels of ACTH, cortisol, insulin, glucose, glycated hemoglobin were studied, tests with dexamethasone and an oral glucose tolerance test (OGTT) were performed; MSCT of the adrenal gland and MRI of the pituitary gland. Fasting glucose (IH), NTG and diabetes were determined according to international criteria (EASD 2019, IDF 2018) Results. It was found that out of 264 patients with SC, 136 (51.5%) had various disorders of carbohydrate metabolism (CM), including diabetes in 32.6 ± 2.9% (86 bp), GTD in 18, 6 ± 2.4% (49 bp) and NGN - in 0.4 ± 0.4% (1 bp). At the same time, diabetes developed in 33.3% of cases in patients with ACTH-DS, 24.4% of ACTH-IS and 75% with ACTH-ESC (p˂ 0.01; p˂ 0.001). Cases of prediabetes were mainly found in the form of NTG in 17.4% of ACTH-DS and 26.8% in ACTH-IS. Conclusions. In the Republic of Uzbekistan, CM took place in the overwhelming majority of patients with CS (51.5%) and clearly depended on the type of CS (ACTH-ES, AKTG-DS, AKTG-IS) and correlated with the degree of hypercortisolism.
SUN-047 Cosmetic Injection of Silicone in a Transgender Person Leading to Granulomatous Disease with Hypercalcemia and Terminal Kidney Failure
Authors: Pereira Cecilia , Villalobos Carolina , Flores Cristian , Crisosto Nicolas
Published: May 2020

Background: Granulomatous disease secondary to cosmetic injection of silicone is an uncommon cause of hypercalcemia. Transgender persons with limited access to appropriate surgery commonly use this procedure as an alternative, which can cause serious complications. Clinical Case: Forty year old transgender women with a 7-year history of nephrolithiasis treated with lithotripsy, pyelotomy and requiring the installation of a pig tail. She is admitted at the emergency room due to renal failure. Non-contrast CT rules out acute obstruction and lab tests conclude terminal kidney failure so she is started with dialysis and discharged. Two months later she returns with fever, she is diagnosed with central venous catheter-related bloodstream infection associated to the dialysis catheter and is started with antibiotics. Physical exam reveals pigmented, indurated nodular areas in her buttocks, hips and legs. The patient is re-interrogated and admits to have had injections of industrial silicone at the age of 22 in the described nodular areas. Regarding her transition process she had a vaginoplasty at 25 years old and was started with estrogens at that time but abandoned controls thereafter. Laboratory: Calcium 10, 8 (8,6-10,2 mg/dl), P 6 (2,5-4,5 mg/dl), PTH 17 (12-88 pg / ml), 25OHVD 3 (30ng / ml). Abdominal and thorax CT showed multiple pulmonary nodules, hilar, axillar and retroperitoneal adenopathies, hepatosplenomegaly, and subcutaneous granulomas with calcification in the buttocks and lumbar areas. HVB, HVC, VDRL and HIV serologies were negative as were ANA, pANCA and Rheumatoid Factor. Myelogram was normal. Biopsy of the involved skin and axillary lymph nodes revealed foreign body granulomatous reaction. Real Time PCR determination of the CYP27B1 mRNA showed a positive expression of this gene in the lesions confirming increased 1 alpha-hydroxylase activity as the cause of hypercalcemia. Tc-99m MDP scintigraphy showed increased activity in the soft tissue of the hips, buttocks and legs. Currently she maintains dialysis with normal values of calcium and is following regular controls in our gender program. Conclusion: Granulomatous disease due to cosmetic injection of silicone is a cause of hypercalcemia that should be suspected in the appropriate context. It is important to educate the transgender community about the possible severe adverse effects of these not authorized procedures.
SAT-668 Liver Function Test in Type 1 Diabetes Mellitus and Prevalence of Other Autoimmune Disease in Type 1 Diabetes Mellitus
Authors: Anusha Nadig , divya sree , sachan alok , suresh v s , Venkatanarasu Ashok
Published: May 2020

Background

Recent studies suggest that non-alcoholic fatty liver disease (NAFLD) may be more common in type 1 diabetes. The pathogenesis of NAFLD has been hypothesized that, hepatic fat accumulation may be due to hyperglycemia induced activation of the transcription factors.

Type 1 DM inducing autoimmune process can also affect other organs. So screening for celiac disease, Hashimoto’s thyroiditis and other autoimmune disorders is necessary.

Aims:

1.

To evaluate the prevalence of NAFLD in type 1 DM. And to correlate glycosylated hemoglobin (HbA1c) with aspartate transaminase (AST) and alanine transaminase (ALT).

2.

To determine the prevalence of autoimmune disease like hypothyroidism, celiac disease, vitamin B12 deficiency and Vitiligo in type 1 DM.

3.

To study the prevalence of microvascular complications and correlate it with HBA1c.

Study design

Cross sectional study

Methods:

Eighty patients with type 1 DM were taken, liver function test, HbA1c and TSH was sent. BMI was calculated. We calculated prevalence of elevated AST and ALT in all patients and correlated with HbA1c.

All patients were screened for other autoimmune disorders. Screening for celiac disease was done by celiac antibodies and antibodies positive patients underwent duodenal biopsy. Thyroid screening was done by TSH and anti TPO antibodies. Vitamin B12 levels were also measured.

Patients also underwent screening for microvascular complications to see its prevalence.

Statistical Analysis

Categorical data was represented in the form of frequencies and proportions. Chi square test was used as test of significance for qualitative data. Continuous data was represented as mean and standard deviation.

Pearson correlation or Spearman’s correlation was done to find the correlation between two quantitative variables and qualitative variables and quantitative variables respectively.

Results:

Mean age of subjects was 21.38 ± 6.16 years, 57.6% were females and 42.4% were males, mean HBA1c was 10.45 ± 2.54, mean AST was 24.71 ± 15.85 and mean ALT was 22.08 ± 15.13. In the study significant positive correlation was observed between HbA1c and ALT, i.e. With increase in HbA1c there was increase in ALT and vice versa. There was no significant correlation between HbA1c and AST.

In the study 21.2% were hypothyroid, 29.4%had Celiac disease, 1.2% had Vitiligo and 23.5% had B12 deficiency. In the study there was no significant association between Micro vascular complications and HbA1c.

In the study 3.5% had neuropathy, 7% had retinopathy, 4.7% had nephropathy.

Conclusion:

Elevated ALT can be associated with NAFLD related risk factors. Type 1 diabetics with elevated ALT should be evaluated. And patients with type 1 DM should undergo screening for other autoimmune disease.
SAT-635 Results of a Preclinical Pilot Study Evaluating 24-Hour Subcutaneous Infusion of the GLP-1 Analogue Liraglutide Delivered via the H-Patch Wearable Device
Authors: Barnes Jessica W , Lucera Erick
Published: May 2020

Nonalcoholic fatty liver disease (NAFLD) affects an estimated 30% of Americans, is the most common cause of chronic liver disease in the US, and a leading cause of liver-related morbidity/mortality worldwide1. Currently, there are no FDA-approved drugs specifically tailored to NAFLD or its big brother, non-alcoholic steatohepatitis (NASH). Glucagon-like peptide 1 (GLP-1) is an incretin peptide hormone, secreted in the distal ileum and proximal colon by L cells. Besides stimulating the pancreas to cause beta cell proliferation and enhance insulin biosynthesis, GLP-1 interacts with receptors in other parts of the GI tract, lung, kidney and CNS. Thus, GLP-1’s metabolic functions include delayed gastric emptying, appetite suppression, enhanced liver glucose uptake, peripheral insulin sensitivity, as well as glucose-dependent insulin secretion while inhibiting the release of glucagon from α-cells. While GLP-1 receptor agonists such as exenatide and liraglutide have been approved for type 2 diabetes, a meta-analysis of several studies has shown promise in patients with NASH. Effects including decreased serum ALT levels, improvement in hepatic fat content and fibrosis, and weight loss making GLP-1 therapeutics potentially attractive for use in patients with NASH and metabolic syndrome2-5. While subcutaneous injection is an avenue for administration, continuous infusion offers many benefits for native GLP-1 and GLP-1 analogues. We investigated the pharmacokinetics (PK) of a GLP-1 analogue (liraglutide) delivered over a single 24h period using the wearable h-Patch™ subcutaneous infusion device in dogs. Liraglutide (1800ug) was infused at a static rate over 24h delivered with PK evaluated at time points to 72h from the start of infusion. Liraglutide levels were detectable in blood detected within 30m of the beginning of infusion, peaked above the upper level of quantitation of the LC/MS/MS analysis (316ng/ml upper level of quantitation), and gradually decreased with quantifiable levels still detected 48h after completion of h-Patch™ infusion. The h-Patch™ provides a simple all-in-one delivery device with no exposed needle, no programming or infusion set required, additionally it can be configured to deliver two payload in separate reservoirs offering the potential option of an insulin/GLP-1 infusion combination. These preliminary encouraging results of liraglutide infusion via the h-Patch warrant further investigation in a variety of indications including diabetes, NASH, and obesity as a monotherapy and in combination with other complementary therapeutics. 1. Liver Int. 2017; 37(S1):97-103. 2. Lancet. 2016; 387(10019):679-690. 3. J Gastroenterol Hepatol. 2016; 31(1):23-31. 4. Clin Ther. 2007; 29(1):139-153. 5. Aliment Pharmacol Ther. 2013; 37(2):234-242.