bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-LB36 Primary Aldosteronism Due Tosimultaneous Occurrence of Aldosteronoma in the Left Adrenal Gland and Ectopicaldosteronoma in the Liver: A Case Report
Authors: He Xiaoying , Huang Zhimin , Ke Weijian , Li Yanbing 
Published: May 2020

Abstract
Rationale: Ectopic adrenal tissue is the adrenal rests along the path from gonads to adrenal glands during embryogenesis. Ectopic aldosteronoma is a rare disease presented with over-production of aldosterone by the ectopic adrenocortical tissue. Diagnosis is a clinical challenge with simultaneous occurrence of ectopic aldosteronoma. To our knowledge this is the first reported case of simultaneous occurrence of aldosteronoma in the adrenal gland and ectopic aldosteronoma in the liver based on literatures. Patient concerns: A 33-year-old woman presented with resistant hypertension and severe hypokalemea for 3 years. 5 months ago, the patient was diagnosed as aldosteronoma in left adrenal gland and underwent right adrenalectomy. The histopathological examination of the resected sample suggested adrenal cortical adenoma. The patient still had symptoms of hypertension and hypokalemia after operation, but the blood potassium level was higher than that before operation (minimum blood potassium level rose from 1.8 mmol/L to 2.6 mmol/L). Diagnosis: The saline load test, captopril test, and plasma aldosterone/renin ratio were indicative of primary aldosteronism (PA). The computed tomographic scan (CT) was suggestive of a low-density mass (2.9×2.2 cm) in the liver which was very near to the right adrenal area. Magnetic resonance imaging (MRI) further confirmed that the lesion was located in the liver. PET-CT eliminated the possibility of metastasis to other parts of the body. Ultrasound guided biopsy confirmed that the tumor was ectopic adrenal tissue in the liver. Interventions: Ultrasound-guided percutaneous radiofrequency ablation was performed to the tumor in the liver.Outcomes: The patient’s blood potassium level was 3.8 mmol/L on the third day after the ablation without any potassium supplementation treatments. On follow-up of 2-weeks duration, the patient has g good control over her blood pressure of around 126/74 mmHg and blood potassium of 4.55 mmol/L, without taking any medications. Lessons: The patient was diagnosed with PA due to simultaneous occurrence of aldosteronoma in the left adrenal gland and ectopic aldosteronoma in the liver, which is very rare. Ultrasound-Guided Percutaneous Radiofrequency Ablation is a safe and effective treatment for ectopic aldosteronoma in liver.
MON-LB123 Diagnosis and Management of Euglycemic DKA in the Setting of SGLT2 Inhibitor Use and Prostate Abscess
Authors: Rameshkumar Naveen Sundar 
Published: May 2020

Abstract
Introduction: SGLT2i has been associated with euglycemic DKA by increasing lipid oxidation and glucagon synthesis. In the event of an underlying infection, increased ketogenesis could lead to the presentation of DKA. Clinical case: A 35 year old male patient who was recently diagnosed with type 2 Diabetes mellitus after he presented to his primary care physician with increased urinary frequency, frothy urine. He was found to have a hemoglobin A1c of 12.5% and blood glucose 408 mg/dl. Urinalysis was negative for nitrites and leukocyte esterase. Patient endorsed to have one sexual partner and safe sexual practices. Urinary gonorrhea and chlamydia antigens were negative. He was diagnosed with diabetes mellitus and was started on ertugliflozin, exenatide and bactrim for possible UTI. Three days later, the patient presented to the ED with dysuria, polyuria, rectal pain, nausea and fatigue. Patient appeared to be in distress with tachypnea and tachycardia. Physical exam showed signs of dehydration. Laboratory evaluation revealed blood glucose at 185 mg/dL. Given the history of recent diagnosis of diabetes mellitus and SGLT2 inhibitor use, euglycemic DKA was suspected. ABG revealed metabolic acidosis (arterial blood gas pH 7.32, pCo2 20, pO2 130) with elevated anion gap of 24, HCO3 level of 10 mmol/L (reference range 22 - 28 mmol/L) and beta-hydroxybutyrate of 5.7 mmol/L (reference range 0 - 0.3 mmol/L). The lactate levels were normal. Wbc count 20,100. Urinalysis showed glucose 4+, ketones 4+, WBC 4, negative for infection. Computed tomography scan of his abdomen and pelvis with contrast showed 3.7 x 2.7 cm prostate abscess and acute cystitis. Patient was treated for euglycemic DKA with infusion of insulin and dextrose 10% with 0.45% NS. Careful monitoring of his blood sugar was required as it dropped with slight increase in infusion rate. He was started on ciprofloxacin for prostate abscess. Patient’s metabolic acidosis resolved and he showed clinical improvement. Endocrinologist was on consult. Patient was switched to insulin regimen for glycemic control. Conclusion: SGLT2i class of drugs has been increasingly used in the treatment of diabetes due to improved cardiovascular outcomes and renal protective effects. However, diagnosing DKA can be a concern while treating patients with this drug. While the SGLT2i is responsible for his euglycemic presentation, DKA was likely triggered by his prostate abscess. They can be used safely with extensive education to the physicians about euglycemic DKA presentation. Management requires starting D10 infusion along with insulin drip to avoid the risk of hypoglycemia.
SAT-LB82 Myxedema as Presenting Feature of Profound Primary Hypothyroidism in a Toddler
Authors: Alradadi Rasha , Eugster Erica A 
Published: May 2020

Abstract
Background: Myxedema is a rare presenting feature of profound primary hypothyroidism that results from disordered accumulation of glycosaminoglycan in the skin and soft tissue. Very few cases of myxedema have been reported in children during the first few years of life.
Clinical Case: A 2-year-old boy with a history of lissencephaly and developmental delay was sent to the emergency room by his primary care physician for worsening of edema. It was noticed by his mother six weeks previously and involved his face, arms, feet and legs. He had no history of cold intolerance, dry skin, hair loss, constipation, or excessive sleep. On exam, he had normal vital signs with no bradycardia and normal blood pressure. Physical exam was remarkable for a sallow complexion, coarse facial features, abdominal distention and non-pitting edema of the face, limbs, hands and feet. A cardiac echo revealed mild pericardial effusion and borderline QT prolongation was noted on EKG. Chest x-ray and abdominal x-ray were unremarkable. Metabolic profile showed normal electrolytes, a mildly low albumin of 2.8 gm/dl and normal renal and liver function. Thyroid function tests were remarkable for an elevated TSH of 562 mcu/ml and a low FT4 of 0.3 ng/dl. TPO and anti-thyroglobulin antibodies were negative. Thyroid ultrasound demonstrated a small thyroid gland in the normal location. Growth data revealed a normal linear growth velocity and weight persistently above the 25th percentile. The child’s newborn screen for congenital hypothyroidism had been normal. He was started on levothyroxine 50 mcg PO per day.
Conclusion: We report an extremely atypical presentation of primary hypothyroidism in a two-year-old boy. He presented with myxedema, pericardial effusions, severe biochemical hypothyroidism and negative thyroid antibodies. The precise etiology and duration of his hypothyroidism, as well as its role in his developmental delay, remain enigmatic. Awareness of unusual presenting features in very young children with hypothyroidism is essential in order to achieve expedient treatment and optimal neurocognitive outcomes.
SUN-LB55 Connect-seq to Superimpose Molecular on Anatomical Neural Circuit Maps
Authors: Hanchate Naresh , Lee Eun Jeong , Ellis Andria , Kondoh Kunio , Kuang Donghui , Basom Ryan , Trapnell Cole , Buck Linda 
Published: May 2020

Abstract
Animals exhibit instinctive behavioral and physiological responses to a variety of stressors to overcome danger and restore homeostasis. The physiological response to stress is governed by hypothalamic corticotropin-releasing hormone (CRH) neurons which regulate the hypothalamic-pituitary-adrenal axis to control blood levels of stress hormones. At present, the neural circuits and signaling mechanisms through which different stress signals are transmitted to CRH neurons are poorly understood. Here, we devised a new method, termed “Connect-Seq,” which couples single-cell transcriptomics and retrograde viral tracing to define the molecular identities of individual neurons in neural circuits. As a proof of concept, using Connect-Seq, we profiled single-cell transcriptomes of 124 brain neurons upstream of CRH neurons and identified subpopulations that are likely to communicate stress-related signals to CRH neurons. Analyses of single-cell transcriptomes for ‘fast-acting’ neurotransmitters revealed subsets of upstream neurons that expressed markers of inhibitory GABAergic neurons or excitatory glutamatergic neurons. Further analyses showed a number of other neuromodulators/neurotransmitters in upstream neurons, including acetylcholine, dopamine, histamine, and 43 different neuropeptides, each expressed in individual neurons or subsets of neurons. These findings reveal extreme molecular heterogeneity among upstream neurons and suggest the upstream neurons use diverse neurochemical messengers to transmit signals to CRH neurons. Many neurons coexpressed different neurotransmitters/neuromodulators, suggesting the co-release of neurochemical messengers. Dual labeling of brain sections verified expression of specific neuromodulators in virus-infected neurons upstream of CRH neurons in selected brain areas. Our results indicate that Connect-Seq can be applied to genetically dissect neural circuits and uncover molecular identities of neurons upstream of specific neuronal types of known function. Molecular markers identified in those neurons lay a foundation for the application of cell-specific genetic tools to investigate the functions and physiological significance of diverse neuronal subsets within complex neural circuits.
SUN-LB57 Assessing the Requirement of Arcuate Nucleus Kisspeptin Neurons in Puberty Onset and Adult LH Secretion
Authors: Coutinho Eulalia A , Esparza Lourdes A , Bolleddu Shreyana , Kauffman Alexander S 
Published: May 2020

Abstract
Puberty is a critical developmental period marking the transition to adulthood and attainment of reproductive capability. A hallmark of puberty is increased pulsatile secretion of pituitary luteinizing hormone (LH) which is itself driven by increased gonadotropin-releasing hormone (GnRH) from the forebrain. The mechanisms governing GnRH neuron activation at puberty still remain unclear, but likely include enhanced stimulation from upstream reproductive neural circuits, including kisspeptin neurons. Kisspeptin is a potent stimulator of GnRH and is required for proper puberty onset. However, the specific brain site(s) from where kisspeptin signaling arises to trigger puberty remain unclarified. Kisspeptin is expressed in two primary nuclei in the hypothalamus, the arcuate nucleus (ARC) and anteroventral periventricular (AVPV) region. Studies suggest that, in adulthood, ARC Kiss1 neurons are involved in driving pulsatile secretion of GnRH (and hence, LH) in both sexes whereas AVPV Kiss1 neurons participate in the preovulatory GnRH/LH surge in females. However, the specific role of either kisspeptin neuron population in puberty onset still remains unknown. We previously showed that both kisspeptin populations show increased Kiss1 gene expression across the pubertal period, yet whether just one or both (or neither) population is needed for puberty to occur has not been determined. Here, we sought to tease out the role—if any—of ARC and AVPV Kiss1 neurons in the pubertal onset process. Since ARC Kiss1 neurons are abundant in both sexes and drive pulsatile GnRH secretion in adulthood, we hypothesized that ARC Kiss1 neurons are necessary for normal puberty onset and, conversely, that AVPV Kiss1 neurons are not sufficient on their own to induce normal puberty. To test this hypothesis, we used a Cre-specific diphtheria toxin approach to ablate just ARC Kiss1 neurons in juvenile mice (~ 2 weeks old) while leaving AVPV Kiss1 neurons intact. Preliminary data thus far indicates that site specific ablation of just ARC Kiss1 neurons during the juvenile period significantly delays puberty onset in both sexes, as measured by vaginal opening, first estrous, and preputial separation. In addition, selective ARC Kiss1 neuron ablation in juvenile life diminishes pulsatile LH secretion levels measured in adulthood, but does not alter LH surge generation in adult females. These preliminary findings empirically demonstrate that, in mice, ARC Kiss1 neurons are required for proper activation of the reproductive axis during puberty but not the LH surge in adulthood, and AVPV Kiss1 neurons are not sufficient to trigger normal pubertal onset.
SAT-LB50 Fahr’s Syndrome: A Rare Neurological Disorder Unmasked by a Psychiatric Illness
Authors: Figueroa Arnaldo Rojas , Garcia Michelle Marie Mangual , Torres Marina Torres 
Published: May 2020

Abstract
Fahr’s syndrome is a rare familial disorder characterized by abnormal accumulation of calcium deposits bilaterally at basal ganglia. It commonly affects middle-aged adults and presents with a range of neuropsychiatric symptoms. The exact prevalence of Fahr’s syndrome is uncertain; however, intracranial calcifications suggestive of this disorder are detected incidentally in approximately 0.3 % to 1.2 % of CT imaging of the brain with a prevalence of 1/1,000,000. It may be idiopathic or secondary to numerous causes dominated by phosphorous and calcium disorders, with the most common etiology being hypoparathyroidism. We report the case of a 27 years old female patient with a medical history of insulin-dependent Diabetes Mellitus type 1, Bipolar disorder, Autoimmune Polyglandular Syndrome Type 1, Thalassemia major, Primary Hypoparathyroidism and Bronchial Asthma who was admitted to the hospital after presenting an episode of dizziness, slurred speech and involuntary movements associated to hypoglycemia. The patient had a medical history of recurrent episodes of conscious self-induced hypoglycemia with double doses of insulin therapy and noncompliance with home medications. Upon evaluation, patient presents aggressive and defiant behavior. Physical and neurological examination was difficult to assess since she refused to be examined. Laboratories were remarkable for serum calcium of 6.2mg/dl, albumin of 3.5g/dl, with corrected calcium levels of 6.5mg/dl, suggestive of severe hypercalcemia. Head CT scan showed bilateral subcortical, basal ganglia clouded, thalamic, and cerebellar calcifications with preserved gray and white matter differentiation. Treatment was tailored to symptoms control and correction of underlying abnormalities. These case present the most critical features of the diagnostic criteria of Fahr’s syndrome. Pathologically, calcifications occur in the vascular walls and in the perivascular spaces of arterioles, capillaries, and veins. Clinical findings of Fahr’s syndrome vary from neurological disorder to those mimicking Bipolar disorder. In this case, there were no neurological symptoms, and this patient only presented with psychiatric manifestations suggestive of bipolar disorder. For any psychiatric condition, it is essential to rule out organic brain disorders before labeling a patient, especially one who is young and has multiple endocrinopathies which could be associated with this rare condition.
SAT-LB61 METTL3 Promotes Sparsely Granulated GH-Secreting Pituitary Adenomas to Behavior as Densely Granulated Adenomas
Authors: Jiang Xiaobing , bian piaopiao , zhang weiyu 
Published: May 2020

Abstract
Background: Growth hormone (GH)-secreting pituitary adenomas can be divided into densely and sparsely granulated subtypes, based on electron microscopic studies. The latter are frequently associated with more invasive behavior, and respond worse to somatostatin analogues. The underlining mechanisms are largely unknown. Increasing evidence showed that N6-methyladenosine (m6A) of messenger RNAs (mRNAs) participated in the development of various tumors. We aimed to investigate the role of RNA m6A modification in the classification of GH-secreting pituitary adenomas. Methods: The main components of m6A methyltransferase complex, demethylase, and RNA m6A levels were compared between sparsely and densely GH-secreting tumors. The role of METTL3 was functionally studied. Results: The level of m6A methyltransferases (METTL3, WTAP and METTL14) and demethylase (FTO and ALKBH5) were significantly downregulated in GH adenomas, comparing to the normal pituitary tissues. However, only METTL3 and METTL14 were shown to significantly higher in densely granulated tumors than those in sparsely ones. Consistently, the level of RNA m6A was markedly increased in densely granulated GH adenomas. In addition, the expression of METTL3 was positively correlated with the level of RNA m6A among tumor samples, and METTL3 silencing decreased RNA m6A of GH3 cells. METTL3 was demonstrated to function as a tumor suppressor based on in vivo and in vitro evidence, using patient-derived and GH3 cells. Moreover, the sensitivity of GH3 cells to pasireotide was increased with METTL3 overexpression, but decreased when METTL3 was silenced. Consistently, METTL3 silencing inhibited GH secretory, and decreased the expression of SSTR2 and SSTR5. Conclusions: METTL3 functions as a tumor suppressor in GH secreting adenomas, and enhance tumor cells sensitivity to medical treatment. Our work uncovers the critical roles of METTL3 in the pathogenesis of GH adenomas, since it potentially promotes the transition from sparsely to densely granulated subtypes.
MON-LB51 Stimulation for Bilateral Inferior Petrosal Sinus Sampling May Be Unnecessary for Diagnosis of ACTH Dependent Cushing Syndrome
Authors: Builes-barrera Carlos Alfonso , Roman-Gonzalez Alejandro , Villada Oscar A , Escudero Pablo 
Published: May 2020

Abstract
Introduction: Bilateral inferior petrosal sinus sampling (BIPSS) is the gold standard test to differentiate Cushing’s disease (CD) and ectopic ACTH syndrome (EAS). Stimulation test for diagnosis may be unnecessary in some cases and the diagnostic yield of the stimulation test may be similar to the basal measurement. Methods: 34 adult patients referred for diagnosis of ACTH dependent Cushing syndrome. Basal simples for prolactin and ACTH were taken from bilateral inferior petrosal sinus and from peripheral vein. Stimulation test with desmopressin (32 subject) or CRH (2 subjects) was performed. Samples were taken at 0, 3, 5 and 10 minutes. To compare the percentage of diagnosis with each measurement the MacNemar test was done. Results: Right basal ACTH was 465 pg./ml (ICR 62-1250), ACTH at 3 minutes was 647 (ICR 227-2610), ACTH at 5 minutes was 1250 (ICR 245-1965), ACTH at 10 minutes was 230 (71-550). Left basal ACTH was 230 (71-550), at 3 minutes was 453 (ICR 116-1250), at 5 minutes was 431 (91-1250), at 10 minutes was 534 (140-1250). Median basal ACTH ratio was 13.8 (ICR 5.1-26), at 3 minutes was 34.5 (ICR 13-82), at 5 minutes was 30.6 (11.4-49.8), at 10 minutes was 18.5 (8.2-48.2). The higher ratio was at 3 minutes. Basal ACTH ratio was &lt;2 in only 4 cases. 2 out of 4 cases had ratio &gt;3 after stimulation test. CD was diagnosed with basal ratio in 88.6% of cases, and at 3, 5 and 10 minutes in 94.3% of cases. There was no difference in percentage of CD diagnosis at 3, 5 or 10 minutes (p=1.0). Discussion: Basal ACTH ratio was able to differentiate CD from ECS in most cases (88.6%). At least one additional sample with CRH or desmopressin stimuli identify 94.3% of CD cases with the higher increases at 3 minutes. Additional stimuli do not improve overall diagnosis, therefore, a basal ratio and additional stimulation test at 3 minutes is enough for CD diagnosis. This may decrease the cost of BIPSS and total duration of the procedure.
SAT-LB57 The Spectrum of Genomic and Transcriptomic Alterations in ACTH-Producing and ACTH-Silent Corticotroph Adenomas
Authors: Lerario Antonio Marcondes , Meredith David , Castlen Joseph , Johnson Lauren M , Catalino Michael , Carroll Rona S , Pallais J Carl , Kaiser Ursula B , Bi Wenya Linda , Laws Edward Raymond , Abreu Ana Paula 
Published: May 2020

Abstract
Corticotroph adenomas (CA) are rare pituitary tumors that impose several challenges in clinical management - CA are difficult to diagnose, often recur, and are associated with high morbidity and mortality. CA are characteristically Tpit-positive and PIT1-negative and comprise ACTH-producing (Cushing’s disease (CD)) and ACTH-silent (AS) classes. The molecular programs contributing to disease pathogenesis in CA are still poorly characterized, largely restricted to the identification of somatic mutations in USP8 in 40-60% of CD adenomas. To more fully characterize the mutational and transcriptional landscape driving both classes of CA, we performed whole-exome sequencing and RNA-seq in 19 CD and 16 AS adenomas. We identified USP8 mutations in 53% of CD (10/19) and 6% of AS (1/16) samples. Strikingly, in 19% of AS tumors (3/16), all exhibiting an unusually aggressive disease course, including two cases with brain metastases, we identified recurrent somatic pathogenic mutations in TP53 and novel loss-of-function mutations in telomere maintenance genes DAXX and ATRX. Furthermore, while all tumors with USP8 mutations (regardless of CD/AS status) exhibited no chromosomal abnormalities as measured by copy-number variation (CNV) and loss of heterozygosity (LOH) analysis, 33% of CD (4/12, including 1 tumor with a DAXX mutation) and 36% of AS (4/11, including all DAXX/ATRX-mutated cases) samples exhibited profound chromosomal instability, characterized by hyperdiploidy, widespread whole-chromosome LOH events, and arm-level breakpoints. Using transcriptome analysis (n=22), we identified three classes of tumors (C1-C3), reflecting these distinct somatic alteration profiles. C1 tumors (n=6) are characterized by chromosomal stability, includes exclusively USP8-mutated CD, and exhibits upregulation of genes involved in metabolic processes and protein acetylation. C2 tumors (n=10) are comprised exclusively of AS (including all TP53- and/or DAXX/ATRX-mutated cases), are characterized by chromosomal instability, and exhibits concordant upregulation of cell cycle programs. Finally, C3 (n=6) contains a mixture of AS and CD cases (including CD without mutations in USP8) and features an expression profile that partly overlap with C1 tumors, but also exhibit higher expression of inflammatory genes. Taken together, our data suggest that CD and AS are distinct molecular subtypes of CA, highlighting the dominant role of USP8 mutations in driving a unique transcriptional program and illustrate for the first time that unlike most cases of CD, AS cases are characterized by profound genomic instability and cell cycle activation, features associated with a more aggressive disease course.