bluuebunny/crossref_metadata_2025_split huggingface dataset:
OR16-03 Metabolic Effects Of Hypothalamic Pomc Neurons Generated Postnatally From Tanycytes On A Pomc Null Genetic Background
Authors: Gahlot Surbhi , Wittmann Gabor , Lechan Ronald M , Low Malcolm J 
Published: May 2020

Abstract
Hypothalamic proopiomelanocortin (POMC) neurons are an integral part of the central melanocortin system and regulate feeding and energy balance in vertebrates. Tanycytes are radial glial-like cells lining the third ventricle that contain a subpopulation of adult stem cells, which can differentiate under specific circumstances into glia and neurons, including POMC neurons. However, the capacity of these stem cell-derived neurons to fully mature and integrate into existing neural circuits of physiological relevance is unknown. This study systematically tested whether Pomc mRNA-positive cells newly generated from tanycyte precursors can differentiate into melanocortin-secreting POMC neurons, integrate into the normal anatomical projection pathways of these cells and rescue the obesity phenotype caused by the loss of Pomc expression in ArcPomcfneo/fneo mice. We generated an inducible compound genetic mouse model by crossing RaxCreERT2 with the Cre-dependent ArcPomcfneo/fneo and LSL-syp-tdTomato alleles. Rax is expressed exclusively in postnatal tanycytes, thereby limiting tamoxifen-induced recombination of the two floxed alleles by CreERT2 to tanycytes. As expected, tamoxifen treatment of the mice at age 4–5 wk recapitulated endogenous Rax expression 16 wk later as observed by red fluorescent tdTomato expression in all tanycytes. In addition, Cre recombinase-mediated deletion of the floxed-neomycin cassette from the neuronal enhancer region of the ArcPomcfneo alleles relieved their constitutive transcriptional silencing. Consequently, tamoxifen treatment consistently generated a significant number of newly generated POMC neurons from tanycytes (~10% of the POMC neurons in a WT mouse), identified by Pomc FISH and POMC/α-MSH immunofluorescence in the soma and established terminal projections to hypothalamic nuclei including the PVH and DMH involved in energy homeostasis. A subpopulation of these neurons also expressed the synaptophysin-tDTomato reporter. We performed serial body weight, food intake, body composition, oral GTT and insulin measurements with the RaxCreERT2/+, ArcPomcfneo/fneo mice and found no significant differences in any of these metabolic variables compared to untreated obese ArcPomcfneo/fneo mice. These data are consistent with previous studies from our lab suggesting that Pomc expression has to be at least ~30% of normal to mitigate the obesity phenotype in Pomc-null mice. In conclusion, we demonstrated that tanycytes are capable of generating mature Pomc-expressing neurons in the hypothalamus of adult mice. However, we propose that determining the underlying mechanisms involved in the generation of hypothalamic POMC neurons from tanycytes and interventions to increase their number, might lead to a novel approach to treat obesity. Nothing to Disclose: SG, GW, RML, MJL
MON-434 Encapsulated Follicular-Variant of Micropapillary Carcinoma Presenting with Distant Bony Metastasis
Authors: Berlioz Ana Ramirez , Patel Richa , Chinnakotla Bhavana , Acevedo Camila Margarita Manrique , Liu John 
Published: May 2020

Abstract
INTRODUCTION The incidence of thyroid cancer has risen steadily over the last decades, in part due to increasing diagnosis of apparently low-risk well-differentiated cancers. The outcomes of well-differentiated thyroid cancers, including follicular variant papillary thyroid carcinoma (PTC), are believed to be quite favorable, with a largely indolent benign course. We examine an encapsulated follicular-variant of micropapillary carcinoma presenting with distant bony metastasis. CASE 55-year-old lady presented to clinic after biopsy of iliac crest (IC) mass revealed thyroid tissue. One year prior she started having dull pain at right hip, attributed to increased physical activity. She noticed a tender “lump” on her right hip. CT revealed destructive right iliac 8 cm mass with extraosseous soft tissue component, central necrosis, and eccentric calcifications; and right ovarian cyst. Right IC biopsy was consistent with thyroid tissue with positive Thyroglobulin and TTF-1 immunostains. Physical exam was normal, except for mild tachycardia, hypertension, right flank large rounded mass fixed to IC, tender to palpation without erythema or warmth on overlying skin. Thyroid ultrasound showed normal thyroid gland except 5.58 x 6.22 x 7.76 mm left lobe nodule without increased vascularity but with coarse peripheral calcification. FNA was unsatisfactory. Thyroid function tests revealed undetectable TSH, elevated FT4, FT3, and markedly elevated thyroglobulin and TSI. PET/CT scan showed focal area of mild FDG avidity, corresponding to the right iliac crest mass, without additional areas of FDG avidity suggestive of metastatic disease or primary neoplastic process. Three weeks after presentation, patient began having symptoms of hyperthyroidism. As FT4 and FT3 continued to rise, she was started on propranolol and methimazole. Due to inadequate response, methimazole was switched to high dose propylthiouracil with mild improvement. Thyroid uptake and scan and SPECT-CT revealed increased thyroid uptake and thyromegaly consistent with Graves’ disease and redemonstrated large right IC lesion with increased uptake in the periphery and central photopenia, suggesting metastatic thyroid malignancy. Pathology from total thyroidectomy reported encapsulated follicular variant of PTC, confined to the left lobe of the thyroid, without extrathyroidal extension, greatest tumor dimension 0.6cm. As metastasis to the IC were unlikely to have originated from this small encapsulated thyroid cancer, it was recommended to proceed with right oophorectomy for suspected malignant struma ovarii and IC lesion debulking. Surgical pathology revealed right ovary and fallopian tube without pathologic changes or features of teratoma and tissue from right iliac mass consistent with PTC. Patient is off all antithyroid medications and remains biochemically euthyroid, awaiting radioactive iodine therapy.
MON-443 SPECT/CT Localization of Incidental Diverticular Bleed After Radioiodine (i131) Therapy for Metastatic Thyroid Cancer
Authors: Doshi Sejal B , Kardan Arash 
Published: May 2020

Abstract
Background: Radioiodine therapy for patients with metastatic papillary and follicular thyroid cancer status post total thyroidectomy improves overall survival and is standard of care. Physiologic and pathologic biodistribution of I131 is dependent on tissue sodium iodine symporter expression with nonspecific radioiodine distribution seen secondary to physiologic routes of excretion.
Clinical Case: Whole body scintigraphy (WBS) was performed seven days after I131 therapy in a 37-year-old male treated for metastatic papillary thyroid cancer with extension to a thyroglossal duct cyst at the time of surgery. His post-procedural course was uncomplicated with the exception of self-limited hematochezia six days after ablation. WBS images demonstrated a focus more superiorly in the neck concordant with metastatic thyroglossal duct cyst involvement. Activity was also present in the small and large bowel distribution reflecting normal routes of radioiodine excretion. WBS images depicted a discrete focus of radioiodine activity in the right lower quadrant, which SPECT/CT further localizes as activity in the sigmoid colon. Non-contrast CT images demonstrate an associated linear pattern of hyperdense hyperattenuation in the colonic lumen consistent with fresh blood. It is well established that the physiologic and pathologic biodistribution of I131 is dependent on tissue sodium-iodine symporter expression with additional distribution secondary to normal routes of excretion. Nonspecific radioiodine localization has been described at sites of inflammation secondary to vasodilation and increased vascular permeability resulting in leakage and accumulation in tissues. Sodium-iodine expression is found in many tissues, including salivary glands, lactating mammary glands, gastric mucosa, thymus, and small bowel; however, they are not expressed in the colon, nasopharyngeal mucosa, or orbital fibroblasts. I131 localization has been previously described within numerous body diverticula, such as Zenker’s and Meckel’s diverticula; however, radioiodine activity in association with an acute colonic diverticular bleed has not been reported.
Conclusion: We propose that the isolated focus of radioiodine activity in the sigmoid colon associated with transient self-limited bleed could be either related to preexisting diverticulitis leading to I131 accumulation secondary to hyperemia, increased vascular capillary permeability, and subsequent aggravation of colonic mucosa resulting in a transient bleed or due to incidental nonspecific pooling of radioiodine in a colonic diverticulum resulting in secondary mucosal irritation with subsequent minor bleeding. To our knowledge this is the first reported case of SPECT/CT localization of radioiodine to an isolated colonic diverticular bleed in a patient status post I131 therapy for metastatic papillary thyroid cancer.
MON-246 A Diagnostic Dilemma of Primary Versus Secondary Thyroid and Adrenal Hormone Insufficiencies: A Unique Case of Widely Metastatic Renal Cell Carcinoma After Brain Radiation
Authors: Gugger Aristea Sideri , Stamatiades George Alexiades , Majumdar Sachin K 
Published: May 2020

Abstract
Background Identifying the etiology of hormonal insufficiency is important for correct diagnosis and for appropriate hormone supplementation. Usually multiple hormone deficiencies are driven by pituitary pathology, but here we present a case that poses a unique diagnostic and therapeutic dilemma. Clinical Case A 55 y/o lady with HTN and recently diagnosed metastatic Renal Cell Carcinoma (RCC) presented with weakness, dizziness, altered mental status, polydipsia and polyuria. Her metastases included the bilateral adrenal glands, thyroid, brain, and she had a sellar lesion displacing the pituitary as well as infundibular thickening. She had been treated with dexamethasone due to vasogenic edema, whole brain radiation, and was going to start immunotherapy (Ipilumimab&Nivolumimab). On exam she had relative hypotension and tachycardia (BP 115/58, HR 108). She was diagnosed with non-PTH mediated hypercalcemia (Ca 13.9/ 15.3 corrected for albumin 2.3, PTH 6.5, PTH-RP 69, Vitamin D-25 19.4). Her calcium normalized after fluid resuscitation and bisphosphonate treatment, but weakness and hypotension persisted. We tested thyroid and adrenal function given the location of her lesions, recent whole brain radiation, and recent steroid use. Her TSH was 0.017 (0.270 - 4.200 µIU/mL), fT4 0.84 (0.80 - 1.50 ng/dL), T3 0.59 (72.0 - 153.0 ng/dL), ACTH was 1.7 (7.2-63.3 pg/ml), cortisol 1.3 (6.0 - 18.4 ug/dL), aldosterone 3 (&lt; or = 28 ng/dL), renin 7.87 (0.25 - 5.82 ng/mL/h), renin/aldosterone 0.4 (0.9 - 28.9). At 30 minutes after cosyntropin administration cortisol was 7.7 ug/dL, aldosterone 26 ng/dL, and at 60 minutes cortisol was 10.3 ug/dL. Hydrocortisone was initiated while tapering off dexamethasone, and levothyroxine was offered but declined. She opted to postpone further workup. Conclusion This patient presents a dilemma in identifying the primary causes of hormonal abnormalities given potential pituitary and primary thyroid and adrenal disease. The thyroid abnormalities could represent sick euthyroid physiology with lower T4 to T3 conversion or the effects of steroids which can also suppress TSH vs. hypothalamic or pituitary disease. Primary hypothyroidism from gland destruction was unlikely. The low ACTH and cortisol levels were expected since she was on dexamethasone, but low aldosterone with raised renin activity was concerning for primary adrenal insufficiency. However, after cosyntropin the suboptimal cortisol yet preserved aldosterone response supported secondary or tertiary adrenal insufficiency, and only cortisol was supplemented. Understanding her endocrine disease had implications for longer term management given that replacement may only need to be temporary and adrenal recovery might be possible. Further, the use of a 30 minute aldosterone level can be helpful in cases where multiple factors and discrepant laboratory findings may exist.
OR15-02 Mental Health Implications and Determinants of When Youth Present to a Gender Clinic
Authors: Sorbara Julia , Chiniara Lyne , Ngo Hazel , Thompson Shelby , Palmert Mark Raney 
Published: May 2020

Abstract
Background/Aims: Gender incongruent (GI) youth experience high rates of mental health comorbidities. While gender-affirming medical care (GAMC) provides psychological benefit, GI youth often present to care at older ages. The goals of this study were to 1) assess the relationship between age at presentation to GAMC and rates of mental health comorbidities, 2) identify factors influencing when youth present to GAMC, and 3) determine whether older presenting youth face more barriers to care.
Methods: We performed a cross-sectional chart review of patients presenting to GAMC. Subjects were classified a priori as younger presenting youth (YPY): &lt;15 years of age at presentation or older presenting youth (OPY): &gt; 15 years of age. Self-reported rates of mental health comorbidities and medication use were compared between groups. Binary logistic regression analysis was used to identify determinants of mental health comorbidities. Covariates included pubertal stage at presentation, social transition status, and assigned sex. Next, we performed a sequential exploratory mixed-methods study. Factors influencing age at presentation to GAMC were explored through 24 semi-structured interviews with OPY, YPY, and their caregivers (OPY-C and YPY-C). Thematic analysis identified themes with differential representation between OPY/OPY-C and YPY/YPY-C. From these themes, a questionnaire was designed and distributed to youth and caregivers presenting for follow-up. Responses were compared between OPY and YPY and between OPY-C and YPY-C.
Results: Of 300 youth, there were184 OPY and 116 YPY. Upon presentation, more OPY than YPY reported a diagnosis of depression (46% vs. 30%), had self-harmed (40% vs. 28%), had considered suicide (52% vs. 40%), had attempted suicide (17% vs. 9%), and required psychoactive medications (36% vs. 23%), all p &lt; .05. After controlling for covariates, late puberty (Tanner stage 4 or 5) was associated with depressive disorders (OR 5.49 [95% CI: 1.14, 26.32]) and anxiety disorders (OR 4.18 [95% CI: 1.22, 14.49]) while older age remained associated only with psychoactive medication use (OR 1.31 [95% CI: 1.05, 1.63]). Six themes were identified from interviews that influenced age at first clinic visit, including individual, environmental, and healthcare system factors. 101/152 youth and 102/147 caregivers completed questionnaires. While OPY/OPY-C did not endorse more barriers to care than YPY/YPY-C, more OPY than YPY had religious families (54% vs 28%, p=.01) while more YPY than OPY had LGBTQ+ family members (46% vs. 20%, p=.006).
Conclusions: Older age and late pubertal stage are associated with worse mental health among GI youth presenting to GAMC. Our findings emphasize the importance of timely access to GAMC for GI youth and highlight familial environment as a factor that influences when youth present to gender-affirmative care.
MON-162 Utility of 24-Hour Urine Cortisone for the Diagnosis of Cushing’s Syndrome
Authors: McGlotten Raven , Paul Namrata , Soldin Steven , Nieman Lynnette K 
Published: May 2020

Abstract
Background: Obesity, diabetes and hypertension are common in the general population, and do not discriminate between patients (pts) with or without Cushing’s syndrome (CS). Thus, Endocrine Society guidelines recommend biochemical testing in pts with multiple features compatible with the diagnosis (1). A 24-hour (d) urine cortisol (UF) is one of the recommended screening tests. However, tandem mass spectrometry (MS/MS) measurement of UF may be less sensitive than immunoassay because of antibody cross-reactivity with cortisol-like compounds. Cortisone (E), the product of 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) inactivation of cortisol, can be measured in the urine (UE) by MS/MS and might improve the sensitivity of UF alone. The goal of this study was to compare the diagnostic utility of UE, UF, their sum (UF+UE) and their ratio (rUF/UE) for the detection of CS.
Methods: We retrospectively reviewed 35 pts evaluated for CS from 1/2017 to 9/2019. UF (reference range (RR), 3.5-45 ug/d) and UE (RR 17-129 ug/d) were measured by MS/MS. CS etiology was later confirmed in 24 pts by pathology and/or tumor localization [14 female; 14 Cushing’s disease, 7 ectopic ACTH secretion (EAS), 3 presumed EAS awaiting surgery; 46 UF and UEs], and was excluded (noCS) in 11 pts followed over time [8 female; 65 UF and UEs with salivary cortisol and/or dexamethasone suppression]. For CS patients with multiple results, the sample with the lowest UF was compared with all available samples from the NoCS group.
Results: Using a single result for each CS pt, the median (range) for UF, UE, UF+UE and rUF/UE were 281 ug/d (34 - 32,444), 358 ug/d (171 - 802), 642 ug/d (232 - 33246) and 0.78 (0.13 - 40.5). By contrast, using all observations in noCS pts, median (range) for UF, UE, UF+UE and rUF/UE were 13.6 ug/d (2.2 - 88.8), 79.5 ug/d (4.9 - 253), 98.2 ug/d (7.1 - 342) and 0.2 (0.05-0.67).
Using the upper RR (or their sum) as a criterion for abnormality, all CS pts had abnormal UE and UF+UE; 45/46 had abnormal UF. In noCS samples, abnormal values were seen in 12/65 UF (3 pts), 14/65 UE (4 pts), and 13/65 UF+UE (3 pts).
The rUF/UE was &lt; 0.70 in all noCS pts and in 9/24 CS patients. Within this group, the UF+UE was &gt; 230 ug/d in two noCS patients (2/3 and 2/7 samples/pt), and in all 9 CS patients, including two with normal UF and two with UF &lt;50% above the RR. Alternatively, a UE &gt; 170 ug/d identified the same noCS and CS patients.
Conclusion: UF remains an important tool for screening of CS. The addition of UE and UF+UE may provide additional information to discriminate CS from noCS in patients with rUF/UE &lt; 0.70. In contrast to CS pts, noCS pt consistently had UF+UE &gt; 230 ug/d or UE &gt; 170/d, underscoring the importance of multiple samples. Additional study, especially of pts with mild hypercortisolism, is needed to determine optimal diagnostic criteria.
1.Nieman L et al. J Clin Endocrinol Metab 93:1526, 2008
SUN-168 Case Series of ACTH-Secreting Pheochromocytoma: Diagnosis and Management
Authors: Tran Anh , Failor Richard A , Hirsch Irl B 
Published: May 2020

Abstract
INTRO
ACTH-secreting pheochromocytoma is rare, posing challenges in diagnosis and management. Here we report two cases with different presentations and pre-operative approaches.
CASES
Patient 1 A 59 yo female who presented for basal cell carcinoma resection experienced hypertensive crisis intra-op and NSTEMI due to stress cardiomyopathy. The patient reported spells of palpitations, diaphoresis, tremors and pallor since 2015. She had elevated plasma metanephrine (M) 19.4 (0-0.49nmol/L), normetanephrine (NM) 24.7 (0-0.89nmol/L), 24-hour urine M 18711 (30-180mcg) and NM 11897 (128-484mcg). Imaging demonstrated a 5.6 x 5.5 x 5.8cm left adrenal mass. After pre-operative alpha and beta blockade, patient underwent left adrenalectomy.
Pre-op 24-hour urine cortisol was checked as part of secondary HTN evaluation and found to be elevated at 219 (3.5-45mcg). She did not have any features of Cushing’s and this was initially felt to be an appropriate stress response. Due to persistent post-op hypotension and a low 10PM random cortisol level of 3.4mcg/dL, which was inappropriate given patient’s clinical status, hydrocortisone was started with subsequent hemodynamic improvement. Our suspicion was that she had an ACTH-secreting pheochromocytoma, which would have resulted in hypercortisolism pre-op, and secondary AI post-op. Pathology report later confirmed ectopic ACTH production with 25% cells positive with immunostaining.
Patient 2 A 48 yo female was admitted for hypertensive urgency with symptoms of palpitations, facial and abdominal swelling, easy bruising and proximal muscle weakness. Her labs showed elevated 24-hour urine epinephrine 115 (0-20mcg), norepinephrine 366 (0-135mcg), plasma M 288 (0-62pg/mL) and NM 475 (0-145pg/mL), and an AM cortisol was 47.9mcg/dL. Aldosterone and renin levels were &lt;1ng/dL and 0.775ng/mL/hr. Imaging revealed 3.4 x 3.1cm right adrenal mass with portal venous phase of 53 HU and no washout. AM cortisol level post 1mg dexamethasone was 62.6mcg/dL with an ACTH level of 222pg/mL. An ACTH-producing pheochromocytoma was suspected. Despite progressive uptitration of alpha and beta blockade, her BP remained poorly controlled. Her blood glucose also increased to 300s range. Ketoconazole 400mg BID was subsequently added to the regimen with rapid and marked improvement in BP and glycemic control. She underwent right adrenalectomy. Post-op plasma M, NM and ACTH were &lt;0.20nmol/L, 0.36nmol/L and &lt;5pg/mL.
DISCUSSION
Within the past 6 months, we have seen 2 cases of ACTH-secreting pheochromocytoma with different clinical symptoms and pre-op courses. Ectopic ACTH secretion may not cause classic Cushingoid features as in patient 1. Failure to recognize ectopic ACTH pre-op can lead to post-op complications such as AI. Patient 2 demonstrates that treatment of the hypercortisolemia may be necessary in order to adequately control BP and glucose levels prior to surgery.
SUN-696 Effect of Night Shifts on Glycemic Variability in Patients with Type 2 Diabetes
Authors: Garieva Mayya Akakievna 
Published: May 2020

Abstract
The analysis of indicators of carbohydrate metabolism and variability of glycemia in patients with type 2 diabetes mellitus working in night shifts was carried out. As model patients with impaired circadian rhythm, the study included 34 patients, railway transport drivers, with shift mode and the presence of night shifts, with work experience of more than 5 years, the duration of type 2 diabetes mellitus (DM2) from 1 to 7 years, who are on oral therapy with hypoglycemic drugs. Simulation of different working conditions (day-night) was carried out in the simulator “driver’s cabin”. All patients underwent a study of the main indicators of carbohydrate metabolism (fasting glycemia, postprandial glycemia, glycated hemoglobin (HbA1c)), as well as continuous daily glucose monitoring (CGMS) using Medtronic MiniMed iPro2 system (from 3 to 7 days).
Target glycemic levels were not achieved: fasting glycemia was 6.98±1.41 mmol/l; postprandial glycemia was 9.57±1.65 mmol/l; HbA1c was 7.23±1.62%.
The analysis of CGMS revealed high variability of glycemic index MAGE-4.88±0.59 mmol/l. also calculated indicators SD - 1.52±0.63 mmol/l; Conga - 3.17±0.54 mmol/l; MODD - 2.27±0.12 mmol/l.
The period of hyperglycemia (glucose value above 7.8 mmol/l) according to the results of CGMS was 43.5% (min 19-max 56). The duration of hypoglycemic States in patients without night shifts was 2.4% within 24 hours (min 0-max 6.6).
Correlation analysis between carbohydrate metabolism and glucose variability revealed a significant strong relationship between the level of postprandial glycemia and modd (r=0.87, P=0.001) and MAGE (r=0.82, P=0.01), and also established a mean significant correlation between the level of postprandial glucose and Conga (r=0.52, P=0.01) and SD (r=0.61, P=0.05).
Fasting glycemia and congas were moderately correlated (r=0.4, P=0.01).
Weak reliable correlation was found only between HbA1c level and Conga variability index (r=0.27, P=0.04).
Conclusions: the results of the study indicate the lack of adequate glycemic control in persons working night shifts, high variability of glycemia, which is an independent risk factor for cardiovascular disease in patients with DM2. The associative relationship of fasting glycemia and postprandial with the indicator of variability Conga shows that glucose fluctuations during the day in patients are constant.