bluuebunny/crossref_metadata_2025_split huggingface dataset:
MON-LB039 Acute Paraneoplastic Cushing’s Syndrome in a Patient With Small Cell Lung Cancer and Co-Incidental Adrenal Adenoma: A Case Report
Authors: Gerhardt Louisa Maria Sophie , Sabath Lisa , Borm Katrin , Capraro Joel , Müller Beat 
Published: May 2020

Abstract
Background: Paraneoplastic Cushing’s syndrome is a rare cause of hypercortisolism associated with high morbidity, especially in patients with small cell lung cancer. Therefore, early diagnosis and treatment are critical.
Clinical Case: Herein we present the case of a 58-year-old man who was referred to the endocrinology department, because of refractory hypokalemia (potassium 2.4 mmol/l; RI: 3.4 - 4.5 mmol/l) despite high potassium supplements and spironolactone therapy. History was remarkable for a metabolic syndrome with newly aggravated hypertension and a 60-pack-year smoking history. The patient reported a 20 kg weight gain in 6 weeks and proximal muscle weakness. On examination, he was overweight (BMI 44.8 kg/m²) with bilateral pitting edema. Other features of hypercortisolism such as striae rubrae, facial plethora or ecchymoses, respectively, were not apparent. Initial biochemical tests showed severe hypokalemia and metabolic alkalosis. Night-time salivary cortisol (205 nmol/l; RI: &lt; 2.5 nmol/l), 24-hour urinary free cortisol (&gt; 4357 nmol/24h; RI: 99 - 378 nmol/24h) and serum ACTH (158 ng/l; RI: &lt; 61 ng/l) were markedly elevated. While the MRI of the head demonstrated no pituitary pathology, the CT of thorax and abdomen revealed a pulmonary mass as well as an incidental right adrenal mass. Bronchoscopic biopsy of the pulmonary mass confirmed the suspected diagnosis of ACTH-producing small cell lung cancer. The dignity of the right adrenal mass remained unclear, since the radiologic features per se could not differentiate between adrenal adenoma and metastasis. Chemotherapy with cisplatin/etoposide and inhibition of steroidogenesis with ketoconazole were initiated, which largely controlled the hypercortisolism. Imaging studies after completion of two cycles of chemotherapy showed a tumor response with regression of the pulmonary mass. The right adrenal mass remained stationary under chemotherapy. Thus, an adrenal metastasis could be excluded as potential cause of the adrenal mass, suggesting an incidental adrenal adenoma as the most likely diagnosis.
Conclusion: Paraneoplastic Cushing’s syndrome requires high clinical suspicion for early diagnosis, since many of the classical clinical features of hypercortisolism may still be absent, even if the underlying cancer is already advanced. In patients suspected to have Cushing’s syndrome a three-step diagnostic approach is recommended: (1) biochemical confirmation of hypercortisolism, (2) differentiation between ACTH-dependant and -independant hypercortisolism and (3) identification of its source. This approach helps avoiding misdiagnosis in patients who have both an ACTH-producing cancer and an adrenal adenoma [1].
References: [1] Lacroix et al. Cushing’s syndrome. Lancet 2015; 386: 913-927.
SAT-LB313 A Unicorn With Double Horns - Metastatic Paraganglioma in a Patient With Beckwith-Wiedemann Syndrome and Hereditary Paraganglioma Syndrome Iv
Authors: Narayanan Anand , Soe Myat , Wheeler Amber L , Fitzgerald Paul A 
Published: May 2020

Abstract
Introduction: Beckwith-Wiedemann syndrome (BWS), a multisystem genomic imprinting disorder in chromosome 11p15.5 region, is an overgrowth syndrome often presenting with macroglossia, abdominal wall defects, hemihyperplasia, enlarged abdominal organs and an increased risk of tumors including neuroblastoma, rhabdomyosarcoma, unilateral Wilm’s tumor, hepatoblastoma, adrenal cortical carcinoma and pheochromocytoma. Six cases of benign bilateral pheochromocytomas and one case of pheochromocytoma with lymph node metastasis in BWS have been described in the literature. We describe the first case of BWS with distant metastatic paraganglioma harboring an SDHB (succinate dehydrogenase subunit B) mutation.
Presentation: A 28-year-old male with BWS whose history included an omphalocele and diaphragmatic hernia in infancy, neuroblastoma resected at age 2, and left carotid paraganglioma (PGL) resected at age 22 presented with abdominal pain. CT A/P with contrast revealed a 3.3 x 4.4 cm hypervascular mass and multiple bone metastases. Workup revealed normal plasma/urine metanephrines, elevated plasma dopamine of 178 pg/ml (normal &lt;20) and elevated chromogranin A of 190 ng/ml (normal &lt;90). 68Ga-dotatate PET CT showed hypermetabolic 4.4 cm mass (SUV 83), right hypopharynx mass (SUV 49), and many dota avid areas throughout the skeleton. The abdominal mass was resected and pathology was consistent with PGL. Due to unusual presentation, patient underwent hereditary cancer genetic testing (67 gene panel) and pathogenic mutation (c.713delT) in the SDHB gene was identified, consistent with hereditary PGL syndrome IV.
Conclusion: While pheochromocytomas and other tumors are commonly found in association with BWS, PGLs are not. This is the first documented case of a patient with BWS having distant metastatic PGL. Malignant transformation of hereditary and sporadic pheochromocytomas and paraganglioma (PPGLs) is more common in SDHx associated PPGLs (&gt;40% of metastatic PPGLs are related to an SDHB mutation). Hereditary PGL syndromes should be suspected in the case of PGLs that are recurrent, early onset (&lt;45 years), extra-adrenal and/or metastatic. With additional genetic testing, our patient with an already rare growth disorder was found to have hereditary PGL syndrome IV caused by a pathogenic mutation in the SDHB gene. This unique case highlights the rationale and importance of systematic genetic cancer screening in the diagnostic evaluation of PPGLs.
SAT-LB310 A Mysterious Multiple Endocrine Neoplasia (MEN) Like Syndrome
Authors: Soe Myat Han , cheng cheng , Liu Chienying 
Published: May 2020

Abstract
Multiple endocrine neoplasia (MEN) is characterized by the occurrence of tumors involving two or more endocrine glands in a single patient. Among the four MEN syndromes, MEN4 due to CDKN1B mutation is characterized by parathyroid and anterior pituitary tumors in possible association with tumors of the adrenals, kidneys, and reproductive organs. We presented a patient with MEN 4 like syndrome without CDKN1B, menin or RET mutations.
74 year old male was diagnosed with acromegaly and primary hyperparathyroidism at age 63. Genetic testing revealed no mutations in menin and RET genes. At age 68, he was diagnosed with renal cell carcinoma (RCC) and at age 70, 2cm left adrenal mass was identified on surveillance computerized tomography (CT). No biochemical workup was pursued. Four years later, he developed hypertensive crisis during spine surgery at our institution. Workup revealed elevated plasma metanephrine (490 pg/ml, normal &lt;57) and normetanephrine (1333 pg/ml, normal &lt;148). CT showed the left adrenal mass increased in size to 4.5 cm. Family history is negative for any endocrine tumors. He underwent repeat genetic testing. Analyses of 133 gene panel reported no germline mutations in menin, RET, CDKN1B, NF12, VHL, SDH and other genes tested but there were variants of uncertain significance (VUS) identified in CHEK2 c.14C&gt;T (p.Ser5Leu) and PTCH2 c.2812G&gt;A (p.Gly938Ser). Patient successfully underwent left adrenalectomy after alpha blockage. Paired tumor-normal sequencing of the resected tumor detected a pathogenic deletion frameshift mutation in NF1 with loss of heterozygosity (LOH) along with copy number alterations with losses in 1p34.1-p11.2, 11p11.2-15.4, 11q14.1-q25 and 17q11.2 (including NF1). VUSs were also detected including CDKN1A C117Y variant, and CHD2P80L. Since germline and tumor testing failed to reveal any known pathogenic variants, whole exome sequencing (pending) will be pursued.
The presentation with RCC, pheochromocytoma, pituitary adenoma and parathyroid adenoma is consistent with a MEN syndrome in this patient despite no known pathogenic MEN mutations detected. Somatic mutation in NF1 is a common finding in pheochromocytoma. The biochemical phenotype of pheochromocytoma (elevated metanephrines) is consistent with cluster 2 tumors of kinase signaling pathway as seen in tumors of MEN syndrome and neurofibromatosis. We hope to gain more insight via whole exome sequencing to evaluate for potential novel gene mutation(s).
SUN-LB72 The Relationship Between Estrogen Exposure and Bone Health in Women With Cystic Fibrosis
Authors: Arora Neha , Wu Malinda , Tangpricha Vin 
Published: May 2020

Abstract
Patients with cystic fibrosis (CF) are at risk for cystic fibrosis-related bone disease (CFBD) characterized by low bone mineral density and fractures. Nutritional status, cystic fibrosis-related diabetes (CFRD), lung health, and sex hormone insufficiency affect CFBD. CF Foundation guidelines recommend exogenous estrogen treatment for women with CFBD and sex hormone deficiency. There is a lack of data regarding effects of exogenous estrogen supplementation on the bone health of CF women. This Emory IRB approved case-control study examined the association of estrogen on bone health in CF women. Data included demographics, sex hormone treatments, CFBD modifiers, and bone mineral density. 35 estrogen exposed subjects were matched 1:2 to 70 estrogen unexposed subjects for age, BMI, and transplant status. Statistical tests analyzed differences in bone health outcomes between the estrogen and non-estrogen exposed groups. At baseline, age, BMI, transplant status, and CFRD were not statistically different (p&gt;0.05) between the two groups. The unexposed group had higher rates of pancreatic insufficiency (p=0.02). The exposed and unexposed subjects did not have statistically significant differences in areal bone mineral density at lumbar spine, femoral neck, or total hip (p&gt;0.05). Our study demonstrates that there are no differences in bone mineral density at 3 different sites between estrogen exposed versus estrogen unexposed women. One limitation is that factors that may also influence bone density including vitamin D status, family history, and severity of CF mutation were not corrected for. Future longitudinal studies should determine if estrogen treatment can increase bone density over time in CF women.
SAT-583 Assessment of Thermoregulatory Pathways Induced in Male and Female Mice Lacking Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) in Response to Cold Acclimation
Authors: Filatov Ekaterina , Short Landon I , Forster Maeghan A M , Harris Simon S , Schien Erik N , Hughes Malcolm C , Cline Daemon L , Appleby Colin J , Gray Sarah L 
Published: May 2020

Abstract
Pituitary Adenylate Cyclase Activating Polypetptide (PACAP) is a peptide hormone known to regulate energy homeostasis1. Mice lacking PACAP are cold sensitive and have impaired adrenergic-induced thermogenesis2-4. Interestingly, Pacap null mice can survive cold housing if acclimated slowly, similar to what was observed in UCP1 deficient mice4,5. We hypothesized that Pacap-/- mice employ alternate thermogenic pathways to compensate for impaired adaptive thermogenesis and assessed shivering thermogenesis and UCP1-dependent and UCP1-independent adaptive thermogenesis in male and female Pacap-/- and Pacap+/+ with cold acclimation (4°C). Assessment of oxidative fibres in skeletal muscles and behavioural observations did not show evidence of prolonged shivering in male or female Pacap-/- mice during cold acclimation compared to Pacap+/+ mice. We did however observe morphological and molecular differences in adipose tissues of Pacap-/- mice compared to Pacap+/+ mice that were distinct in males and females. Cold-acclimated, female Pacap-/- mice had decreased induction of UCP1 protein in intrascapular brown fat (iBAT), yet had a significantly higher beiging and UCP1 immunoreactivity (ir) in gonadal white fat (gWAT) compared to female Pacap+/+ mice. Furthermore, beiging was observed in inguinal white fat (ingWAT) and gWAT of female Pacap-/- mice housed at thermoneutrality (30°C), a finding not observed in Pacap+/+ control mice. Unlike female mice, we did not observe impaired UCP1 induction in iBAT of male Pacap-/- mice compared to Pacap+/+ mice, and this was associated with negligible UCP1-ir in male gWAT similar to wildtype controls. Despite previous work that has established impaired adaptive thermogenesis in Pacap-/- mice4, we show here that UCP1 protein can be induced in adipose tissues of Pacap-/- mice during cold acclimation, although to a lesser degree or in a different pattern compared to Pacap+/+ control mice. Taken together, this work suggests that while PACAP is clearly involved in regulating thermoregulation, it is not required for cold-induced UCP1 expression. In addition, this work highlights sexual dimorphism in adipose tissue remodeling and induction of thermogenesis with cold acclimation. References: (1) Rudecki AP, et al. Trends Endocrinol Metab. 2016;27(9), 620–632. (2) Gray SL, et al. J Mol Endocrinol. 2001;15(10), 1739–1747. (3) Gray SL, et al. J Endocrinol. 2002;143(10), 3946–3954. (4) Diané A, et al. J Endocrinol. 2014;222, 327–339. (5) Golozoubova V, et al. FASEB J. 2001;15, 2048–2050.
SAT-LB105 A Transcribed Ultraconserved Noncoding RNA, Uc.336-As, Promotes White to Brown Conversion in 3T3-L1 Cells
Authors: He Xiaoying , Xiang Tao , Guan Hongyu , Li Yanbing 
Published: May 2020

Abstract
Brown adipose tissue (BAT) has gained its popularity since it shows great potential in counteracting obesity and metabolic diseases development. Transcribed ultraconserved regions (T-UCRs), a novel class of long non-coding RNA (lncRNAs), have been implicated in regulating diverse biological processes, including the process of white fat browning. However, the functional and mechanistic details of T-UCRs in the browning process are poorly understood. Here, we identified that a T-UCR, uc.336-as, played an important role during the browning process. Uc.336-as was significantly elevated during browning process induced by glucagon-like peptide-1 receptor agonist (exendin-4) or β3-adrenergic agonist (CL316,243). Overexpression of uc.336-as reduces the differentiation of 3T3-L1 preadipocytes into white adipocytes (inhibited lipid accumulation and decreased the expression of several adipogenesis markers) and induces brown characteristics during differentiation of 3T3-L1 preadipocytes (spurred browning adipocytes phenotypes and increased the expression of the browning associated genes). Moreover, we found that uc.336-as inhibited adipogenesis and promoted browning process via influencing the serine/threonine kinase (AKT)-mammalian target of rapamycin (mTOR) axis, an essential signal pathway in adipocyte metabolism. Taken together, our data show that uc.336-as acts as a negative regulator in white adipocyte differentiation and promotes the browning process, suggesting a potential therapeutic role for uc.336-as in controlling obesity.
SUN-LB117 Faster Acting Insulin Aspart in Patients With Gestational Diabetes Mellitus - an Early Experience From India
Authors: Bhattacharyya Supratik 
Published: May 2020

Abstract
Aims: This study was undertaken to assess the effectiveness and safety of faster acting insulin aspart in patients with gestational diabetes. Though faster acting insulin aspart is approved to be used in pregnancy by regulatory bodies like USFDA, EMA and DCGI (India), no data is published till date on its usage in pregnancy. Settings and Design: An open-label, nonrandomized, and observational study conducted at single centre at Kolkata, India. Subjects and Methods: A total of 37 patients with gestational diabetes mellitus (GDM) were included in the analysis. Patients were started on insulin therapy (faster acting insulin aspart ± basal insulin) once medical nutrition therapy for 2 weeks failed to achieve control, that is., fasting plasma glucose ≥90 mg/dL and/or 1.0 h postprandial plasma glucose ≥130 mg/dL. Basal insulin dose was titrated to achieve a fasting of 90-100 and the Faster aspart was titrated to achieve a post-meal of 120 and not exceeding 130. Patients were followed once every 4 weeks until the 28th week, then once every 2 weeks until 32nd week, then once every week until delivery, and the final visit was on 30 ± 7 days after delivery of the child. Results: Out of 37 full term deliveries, only two had macrosomia. No congenital defects were noted in the anomaly scan and at births. There were no episodes of neonatal hypoglycemia reported. Only one episode of post-meal symptomatic maternal hypoglycemia was reported. Mean number of FiASP injections per day was 2.88 ± 0.39. Mean daily dose of FiASP used was 22.7 ± 6 international units. A total of 89% of the patients received faster aspart thrice daily and remaining received it twice daily. Conclusions: Faster acting insulin aspart was found safe in pregnancy, however, more studies with double-blind, standard controlled studies are required to confirm the findings of this study.
MON-LB86 The Sensitivity and Specificity of Various Thyroid Nodule Ultrasound Characteristics and the Diagnostic Accuracy of the ATA Guidelines and ACR TI-RADS for Predicting Thyroid Cancer at an Urban Endocrinology Clinic
Authors: Dacuycuy Leonierose , Gurung Purnima , Bao Ginny W , Chen Tony , Sudat Sylvia , Yin Anthony York Yul 
Published: May 2020

Abstract
Introduction: Several current guidelines assess sonographic features to guide management of thyroid nodules. The ACR uses an additive point system to assign the level of risk to various sonographic features, whereas the ATA groups sonographic features together to determine the level of risk. The purpose of this study is to compare the performance of the ATA guidelines and ACR TI-RADS at an urban endocrinology clinic in risk stratifying thyroid nodules by their specific sonographic features.
Methods: This retrospective, chart-review study includes adult patients who met sonographic criteria for fine needle aspiration (FNA) biopsy based on ATA or ACR TI-RADS at an outpatient endocrinology practice in San Francisco, CA between December 2011 and August 2019. Patients with a prior history of thyroid malignancy (anaplastic and medullary thyroid carcinoma or thyroid lymphoma) were excluded. The reference standard for the diagnosis of malignancy was surgical pathology or FNA cytology Bethesda category V or VI when surgical pathology was unavailable. Analysis of guideline performances and specific sonographic features included: sensitivities (Sn), specificities (Sp), positive predictive values (PPV), negative predictive values (NPV), and area-under-the-curve (AUC) using Fisher’s exact test.
Results: Two hundred seventy-five nodules among 195 adults (86.2% were women) were included in the analysis. Twelve nodules were malignant, with an associated malignancy rate of 4.4%. TI-RADS had higher accuracy based on AUC of 0.710 compared to 0.623 using ATA guidelines. TI-RADS also had a higher PPV of 21.4% among nodules with 9 points, versus 5.8% among nodules in the ATA “high suspicion” category. Ultrasound characteristics with the highest Sp, relative PPV and NPV were: microcalcifications (84.5%, 4.3%, 96.0%, respectively), taller-than-wide (81.7%, 7.1%, 96.7%), irregular margins (77.7%, 6.0%, 96.5%); the characteristic with the highest Sn was hypoechogenicity (83.3%), however this had relatively low Sp (25.4%) and PPV (4.5%).
Conclusions: TI-RADS performed better with higher overall accuracy and PPV when applied to nodules classified as having the highest malignancy risk. Taller-than-wide shape, irregular margins, and microcalcifications were the characteristics most useful for malignancy risk stratification. Limitations of this study include: interobserver bias, small sample size, referred patient population (which may differ from other institutions), and inability in some cases to confirm malignant FNA cytology with surgical pathology.
SUN-LB88 Thyrotoxic Periodic Paralysis in Hispanic Patients
Authors: Sarwar Tahira , Martinez Jose , Kirupakaran Johnathan , Rodriguez Giovanna , Bahtiyar Gül 
Published: May 2020

Abstract
BACKGROUND: Thyrotoxic periodic paralysis (TPP) presents as acute intermittent attacks of weakness related to hypokalemia, commonly reported in Asians and rare in Hispanics(1). Patients with TPP will have triiodothyronine (T3) triggered increased Na+/K+ ATPase pump activity and transcription of the KCNJ18 gene that encodes for the Kir2.6 channel(2). This permits insulin, catecholamines, stress and alcohol(3) to increase cellular intake of potassium, which causes depolarization and leads to weakness and paralysis. We report a case of TPP in a young Hispanic man who presented with lower extremity weakness and falls. CASE PRESENTATION: A 34-year-old Hispanic man with Graves’ disease, non-adherent to medications presented with generalized weakness, more pronounced in legs, and recurrent falls. Physical examination was unremarkable except for mild enlargement of thyroid gland and abnormal gait due to weakness. Laboratory data showed hypokalemia of 1.8 mmol/L (3.7-5.1 mmol/L) and a TSH level of &lt;0.004 mIU/L (0.34-5.6 mIU/L). Free T4 3.74 ng/dL (0.6-1.6 ng/dL), free T3 597 pg/dL (230-420 Pg/dL), thyroid stimulating Ig 148 (&lt;130). Electrocardiogram did not show U waves. Radio iodine 123 scan of thyroid revealed diffusely increased 24-hour radioactive uptake of 66.5% (10-30%). The patient was diagnosed with TPP and supplemented with three doses of potassium 40 mEq IV infusion. Methimazole and metoprolol were started. He made a good clinical recovery within days. After discharge, he was treated with I-131 (13 mci) and developed postablative hypothyroidism on long term. He was euthyroid on levothyroxine. He did not have any recurrence of weakness at 7-year follow-up. CONCLUSION: TPP is uncommonly seen in Hispanics patients as opposed to Asians(3). Physicians should consider TPP as part of the differential diagnosis in young hyperthyroid Hispanic men presenting with weakness or paralysis, as early recognition and treatment can reduce recovery time and potentially prevent tachyarrhythmia or death. REFERENCES: 1. Matta A, Koppala J, Gossman W. Thyrotoxic hypokalaemic periodic paralysis: a rare presentation of Graves’ disease in a Hispanic patient. BMJ Case Rep. 2014;2014. 2. Ryan DP, Ptacek LJ. Mutations in Potassium Channel Kir2.6 Cause Susceptibility to Thyrotoxic Hypokalemic Periodic Paralysis. Cell, 140(1), pp.88-98. 3. Amblee, A. and Gulati, S. (2016). Thyrotoxic Periodic Paralysis: Eight Cases in Males of Hispanic Origin from a Single Hospital. AACE Clinical Case Reports, 2(1), pp.e58-e64.