bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-521 Hyperemesis Gravidarum Resulting in Wernicke’s Encephalopathy and Abnormal Thyroid Function Tests
Authors: Merrill Jennifer D , Roomiany Pahresah , Wachter Adam , Setji Tracy Lynn 
Published: May 2020

Abstract
Background: Wernicke’s encephalopathy (WE) is a potentially fatal consequence of thiamine deficiency that must be considered in patients with poor nutrition and altered mentation. We report a case of a female with hyperemesis gravidarum (HG), nystagmus, clonus, and abnormal thyroid function tests associated with WE. Clinical Case: A 23 year-old healthy G2P0010 woman was admitted for rehydration at 15 weeks gestation after four weeks of intractable vomiting. She denied medications, supplements and alcohol use. Vitals were normal. Exam showed a fatigued ill appearing female with no thyromegaly, tremor, lid lag, or stare. She had a gravid uterus but otherwise normal exam. Fetal heart rate was normal. Laboratory findings included hyponatremia, hypokalemia, elevated creatinine and transaminases, and normocytic anemia. Hepatitis panel, vitamin B12, ammonia, urinalysis and ultrasound of the appendix and gallbladder were unremarkable. She was treated with intravenous fluids and potassium. Electrolyte abnormalities and renal dysfunction resolved. On hospital day three, she became lethargic, tachycardic, unable to follow commands, and exhibited nystagmus and clonus. Thyroid studies showed TSH 0.06 uIU/mL (0.34 - 5.66 µIU/mL), and free T4 3.59 ng/dL (0.52 - 1.21 ng/dL). Methimazole and propranolol were started while awaiting repeat thyroid studies. MRI brain was not obtained due to aspiration risk. EEG showed diffuse slowing but no epileptiform activity. She returned to baseline mentation within hours of intravenous thiamine, with resolution of dysphagia and nystagmus. Thiamine level returned low (51 nmol/l; normal 67–200 nmol/L). Methimazole and propranolol were stopped and thyroid function tests normalized. She was discharged and delivered a healthy baby at term. Conclusion: WE is an acute neuropsychiatric condition caused by thiamine deficiency. Early recognition and treatment are critical to prevent irreversible damage; the classic signs are ataxia, ophthalmoplegia, and encephalopathy. Historically considered in patients with a history of alcohol use, WE is increasingly recognized in other conditions associated with dietary deficiency, since body stores of thiamine last only 18 days. WE has been reported in HG due to prolonged vomiting and increased thiamine requirements in pregnancy. WE has been associated with thyrotoxicosis, possibly due to increased metabolic demands. Both gestational transient thyrotoxicosis and HG are associated with markedly elevated HCG and present in the first 16 weeks of pregnancy. Initial thyroid studies were concerning for thyrotoxicosis, but normal repeat studies argue against that as a contributor. WE is a life threatening complication of poor oral intake, which should be empirically treated with thiamine prior to glucose. WE may be associated with thyrotoxicosis.
SUN-910 High Enhancement Washout by CT Imaging Does Not Exclude Pheochromocytoma/Paraganglioma: Review of Two Cases
Authors: Erenler Feyza , Lechan Ronald M 
Published: May 2020

Abstract
Background:
It is well known that delayed images from contrast-enhanced CT are useful in distinguishing adrenal adenomas from non-adenomas, with an absolute washout that exceeds 60% being most consistent with a lipid rich adenoma. We present two cases of an adrenal mass that met the criteria for a lipid rich adenoma by CT imaging, but found to be a pheochromocytoma (PCC) and paraganglioma (PGL).
Clinical Case
Case#1
An 82 yo woman presenting with tachycardia was found to have a 2.4 cm heterogeneously attenuating, left adrenal nodule with an absolute washout of 61% and a relative washout of 45%. The right adrenal was normal. Urinary catecholamine levels were elevated with an epinephrine (E) 38 mcg (2–24), norepinephrine (NE) 388 mcg (15–100), dopamine (DOPA) 175 mcg (52–480), metanephrine (MN) mcg 620 (90–315), normetanephrine (NMN) 1553 mcg (122–676) and vanillylmandelic acid 12.5 mg (&lt; 6) on a 24h collection. Due to a cardiac resynchronization therapy device, an MRI could not be obtained. MIBG imaging was obtained and showed increased uptake in left adrenal gland, corresponding to the lesion identified on CT. The patient underwent laparoscopic adrenalectomy and the pathology confirmed a PCC.
Case#2:
A 74 yo man was found to have an incidental right adrenal nodule on CT imaging measuring 2.4 cm. Absolute washout was 83% and relative washout 68%. The left adrenal gland was normal. A follow up MRI obtained showed slight increase in T2 weighted images and no drop out on out of phase imaging, raising concern for a PCC. Urinary catecholamines were elevated including E 12 mcg (2–24), NE 280 mcg (15–100), DOPA 246 mcg (52–480), MN 175 mcg (90–315) and NMN 1298 mcg (122–676) on a 24-hr. collection. MIBG imaging further confirmed the diagnosis with increased uptake in the right adrenal gland. The patient underwent laparoscopic adrenalectomy then, converted to open right adrenalectomy through an anterior approach due to adherence of the tumor to the renal vein. The pathology revealed a PGL.
Conclusion:
PCC/PGL are rare but life-threatening neuroendocrine tumors that require early detection to reduce associated morbidities and mortality and improve surgical outcomes. CT is commonly used to characterize adrenal lesions and an absolute washout of &gt;60% is most consistent with an adenoma. However, as demonstrated by these two cases, washout exceeding 60% can also be seen in non-adenomas, perhaps secondary to degeneration of the nodule causing necrotic or cystic changes or uncommonly, the presence of a high lipid content in the tumor [1]. Thus, when clinical suspicion is strong and/or there is a positive biochemical workup, confirmatory imaging should be considered to establish the diagnosis.
References:
[1] Blake, M. A., Kalra, M. K., Maher, M. M., Sahani, D. V., Sweeney, A. T., Mueller, P. R., ... & Boland, G. W. (2004). Pheochromocytoma: an imaging chameleon. Radiographics, 24(suppl_1), S87-S99.
SUN-247 GABA Receptor-Dependent Inhibition and Excitation of GnRH Neuron Dendrons near the Median Eminence in Mice
Authors: Liu Xinhuai , Porteous Robert , Herbison Allan Edward 
Published: May 2020

Abstract
The gonadotrophin-releasing hormone (GnRH) neuron cell bodies are scattered throughout the basal forebrain but funnel their projections to the median eminence to control fertility in all mammals. In mice, these long projections, termed “dendrons”, have characteristics of both dendrites and axons and are found to receive large numbers of synaptic inputs just prior to entering the median eminence. While the effects of many neurotransmitters have been documented at the GnRH neuron cell body, very little is known about the neural control of the distal dendron.
To examine the role of amino acid neurotransmitters in the regulation of the thin GnRH neuron distal dendrons, we used confocal microscopy in combination with real-time GCaMP6 calcium imaging in acute horizontal brain slices. Adult male and female GnRH-Cre mice were given stereotaxic injections of a Cre-dependent AAV expressing GCaMP6s and, &gt; 3 weeks later, the brain removed and a single thick horizontal brain slice prepared that included the base of the brain and median eminence. The intracellular calcium levels of multiple dendrons were monitored simultaneously while puffs of amino acid receptor agonists were applied. Surprisingly, GABA exhibited a dual action on calcium concentrations with an initial transient increase followed by a prolonged decrease and subsequent rebound. The administration of GABAA and GABAB receptor agonist and antagonists revealed that the transient increase resulted from a quickly desensitizing activation of GABAA receptors while the decrease and subsequent rebound was dependent upon the slower kinetics of the GABAB receptor. Kisspeptin exerts a potent long-lasting elevation of calcium levels in GnRH dendrons and this was robustly inhibited by subsequent GABAB receptor activation. In contrast to GABA, glutamate was not found to have any impact on intracellular calcium levels in the distal dendrons and, similarly, the activation of NMDA or AMPA receptors was found to be ineffective.
The results show that GABA exerts particularly potent modulatory actions upon basal and evoked calcium concentrations within the GnRH neuron distal dendron. This suggests that acute brief activation of the dendron by GABA would facilitate GnRH release through GABAA receptor activation whereas prolonged GABA release would suppress activity through the GABAB receptor. As such, GABA inputs to the distal dendron appear likely to play a major role in the control of GnRH secretion in the mouse.
MON-483 Familial Dysalbuminemic Hyperthyroxinemia with False Hypercortisolemia
Authors: Chiba Koki , Kameda Hiraku , Nomoto Hiroshi , Cho Kyu Yong , Nakamura Akinobu , Jin Shigeki , Matoba Kotaro , Miyoshi Hideaki , Atsumi Tatsuya 
Published: May 2020

Abstract
Background: Familial dysalbuminemic hyperthyroxinemia (FDH) is an autosomal dominant disease characterized by hyperthyroxinemia without symptoms of thyrotoxicosis, due to a high affinity of mutant albumin for thyroxine. No report has described cortisol-albumin binding in FDH patient, and here we present a case of FDH presenting with false hypercortisolemia.
Clinical Case: A 46-year man, previously diagnosed with FDH by genetic test (1), was pointed out hypercortisolemia with normal ACTH level (ACTH 64.7 pg/mL, Cortisol 34.7 μg/dL) during the investigation for Parkinson’s syndrome and referred to our department for further examination. Cortisol was 7.1 μg/dL at midnight, 14.9 μg/dL after low dose dexamethasone overnight test, and DDAVP test was positive. ACTH and cortisol responded to CRH load, although basal and peak cortisol levels were high (35.4 and 53.9 μg/dL, respectively). High dose dexamethasone overnight test showed suppressed ACTH and cortisol, and MRI showed no obvious pituitary adenoma.
In spite of significant high cortisol level, no Cushing sign’s or metabolic abnormalities were observed and urinary free cortisol was within the normal range (30.7 μg/day), suggesting the presence of factors affecting the laboratory testing. We removed albumin from serum with immunoprecipitation using anti-albumin antibody and measured cortisol with LC-MS/MS. The decrease of cortisol was 4% in control serum but 38% in the patient serum after removing albumin, suggesting the binding rate of cortisol to mutant albumin in the patient was increased, leading to false hypercortisolemia.
Conclusion: This is the first case demonstrating the false hypercortisolemia in a FDH patient. Clinicians should consider the possibility of the abnormal cortisol binding to albumin in differential diagnosis of hypercortisolemia with normal ACTH level.
Reference: (1) Norio Wada, et al: A Novel Missense Mutation in Codon 218 of the Albumin Gene in a Distinct Phenotype of Familial Dysalbuminemic Hyperthyroxinemia in a Japanese Kindred. Journal of Clinical Endocrinology and Metabolism 1997;82;3246–3250
MON-060 P-450 Oxidoreductase Deficiency with Antley Bixler Phenotype: A Novel Mutation
Authors: Kumar Anshul , Mathur Sandeep Kumar , Sharma Balram , Purwar Naincy , sharma Himanshu , Saran Sanjay 
Published: May 2020

Abstract
Introduction
We present first case of 46 XY Disorder of Sex Development (DSD) from India due to P-450 Oxidoreductase Deficiency with Novel variant (p.Ala541Thr) in a heterozygous state.
Case Discussion
6 months old boy presented with ambiguous genitalia since birth. No history of neonatal crisis, failure to thrive and pigmentation of skin, maternal virilisation or drug ingestion during pregnancy. On examination: weight 6.2 Kg (3rd centile), height 64 cm (3rd centile), MPH-170 (25-50th centile), head circumference 38 cm (−2.7 SD), vitals stable, trigonocephaly with fused anterior and posterior fontanelle, prominent pointed forehead, midfacial hypoplasia, up slanting eyes, hypertelorism and low set ears were present. Genitalia: 1.5 cm phallus like structure with foreskin, chordee, single perineal opening in form of peno-scrotal hypospadias, bifid scrotum with poor rugosity and poor pigmentation and both gonads (1 ml) were palpable in labio-scrotal fold with external masculinization score (EMS), 6/12 and Prader stage 4.
Investigations showed normal electrolytes and blood sugar, High basal ACTH, post stimulation cortisol 14mcg/dl, Basal 17-OHP was 8.6 ng/ml and post stimulation 12ng/ml, with low DHEAS 36.4 mcg/dl and androstenedione 0.42 ng/ml, LH 16.09 mIU/ml (elevated), FSH 2.97 mIU/ml (normal) and low Testosterone for his age. T/DHT 9.6 (normal&lt;10) and Testosterone /Androstenedione ratio 0.95 (normal &gt;0.8). Abdominal and Pelvic imaging showed normal adrenal glands and absent female internal genitalia, bilateral testis in labio-scrotal fold (right testis-6x6.5x11 mm, left testis-6.6x7x10 mm), corpora cavernosa and bifid scrotum. NCCT Head showed metopic craniosynostosis with trigonocephaly and hypotelorism. Skeletal survey showed bowing of femora. 20 cell Karyotype of peripheral blood lymphocyte was 46 XY. NGS was done of the POR gene, which revealed a heterozygous missense variation in exon 13 of the POR gene variant (p.Ala541Thr) which has not been reported yet.
The patient was initiated hydrocortisone, fludrocortisone, DHT gel and corrective surgery is planned.
Clinical learning
Although in PORD classically the inheritance is generally autosomal recessive, but manifesting heterozygotes are not uncommon1. This case also shows the value of Next gen sequencing and the role it can play in DSD
1. Scott RR, Gomes LG, Huang N, Van Vliet G, Miller WL. Apparent manifesting heterozygosity in P450 oxidoreductase deficiency and its effect on coexisting 21-hydroxylase deficiency. J Clin Endocrinol Metab. 2007;92:2318–2322
OR12-05 MDC1 Is a Novel Estrogen Receptor Co-Regulator in Invasive Lobular Carcinoma of the Breast
Authors: Bordeaux Evelyn K , Sottnik Joseph L , Goodspeed Andrew E , Ferrara Sarah E , Costello James C , Sikora Matthew J 
Published: May 2020

Abstract
Invasive Lobular Carcinoma (ILC) is the 2nd most common histotype of breast cancer, but is critically understudied. ~95% of ILC are estrogen receptor (ER) positive, and previous studies demonstrate the importance of estrogen in ILC etiology. However, retrospective studies show that anti-estrogens are substantially less effective in ILC than in ER+ Invasive Ductal Carcinoma (IDC). This strongly suggests that regulation of ER function is unique in ILC, and we hypothesize that this is due to an ILC-specific cohort of ER co-regulators. We performed Rapid Immunoprecipitation Mass Spectrometry of Endogenous Proteins (RIME) to determine ILC-specific ER-interacting proteins, and identified Mediator of DNA Damage Checkpoint 1 (MDC1) as a novel ER co-regulator in ILC cells. We confirmed ER:MDC1 interaction by co-immunoprecipitation and proximity ligation assays (PLA); interaction was specifically observed in ILC cell lines but not IDC cell lines. Consistent with co-regulator function, we found MDC1 is essential for ER-driven proliferation of ILC cells. MDC1 knockdown dysregulates transcription of ER target genes in ILC cells (e.g. IGFBP4, WNT4). Moreover, RNA-seq analysis showed that in ILC cell line MDA MB 134VI, &gt;50% of ER target genes require MDC1 for their regulation. To understand how MDC1 controls ER transcriptional activity, we performed ChIP-qPCR and found that MDC1 controls ER binding to DNA in ILC cells. Further, MDC1 controls binding of the pioneer factor FOXA1 to DNA, and Dual PLA studies of ER:MDC1 and ER:FOXA1 interaction revealed that MDC1 knockdown decreased ER:FOXA1 interaction. MDC1 canonically functions in DNA damage response, but our preliminary data suggest MDC1 is decoupled from its canonical role in DDR in the context of ER co-regulator activity in ILC cells. Together, these data suggest MDC1, independent of its role in DDR, acts as a novel ER co-regulator in ILC and regulates ER:DNA binding and ER transcriptional function to drive ILC cell proliferation and survival.
MON-011 NALCN Expression Is Regulated by Progesterone and Estrogen in Human Myometrial Smooth Muscle Cells
Authors: Amazu Chinwendu , Ma Xiaofeng , Henkes Clara , Ferreira Juan J , Santi Celia , England Sarah 
Published: May 2020

Abstract
During pregnancy, the uterus transitions from a quiescent state to a highly contractile, excitable state. Both ion channels and hormones are essential for this transition. We recently identified that the Na+ leak channel, non-selective (NALCN) contributes to a leak current in human MSMCs and mice lacking NALCN have prolonged and dysfunctional labor. Additionally, NALCN levels change throughout mouse pregnancy suggesting regulation by hormones of pregnancy, specifically estrogen and progesterone. Here, we tested the hypothesis that P4, a pro-quiescent hormone, and E2, a pro-contractile hormone, regulate NALCN expression and current in the myometrium. In a human immortalized myometrial cells (HM6ERMS2), using qPCR we measured a 2.3 fold decrease and a 5.6 fold increase in NALCN mRNA expression in the presence of E2 and P4, respectively. These findings were also confirmed when NALCN protein expression were measured by immunoblot. Conversely, treatment with the ER antagonist, ICI 182,780, significantly increased NALCN mRNA expression, while treatment with the PR antagonist RU486 significantly decreased NALCN mRNA expression suggesting E2 and P4 work through their respective receptors to regulate NALCN. P4 differentially regulates myometrial activity depending on which progesterone receptor is activated: PRA, promotes contractility, whereas PRB promotes quiescence. Thus to study the effect of each PR, we used a human myometrial cell line stably expressing PRA or PRB, and measured similar increases in NALCN mRNA expression in both cell lines treated with P4. To determine the functional consequences of E2 and P4, we measured NALCN-dependent leak current in MSMCs using whole cell patch clamping. We observed that E2 significantly inhibited while P4 significantly enhanced NALCN current. Finally, we identified estrogen response and progesterone response elements (ERE and PRE) in the NALCN promoter and showed that the PREs contributed to P4 regulation while the ERE did not contribute to the regulation of NALCN expression using luciferase based promoter assays. Overall, our findings show that NALCN is upregulated by P4, the pro-quiescent hormone, and downregulated by E2, the pro-contractile hormone. This data reveals a new mechanism by which NALCN is regulated in the myometrium and may suggest a novel role for NALCN during pregnancy. Further investigation into these novel roles can provide an insight into potential targets to modulate uterine quiescence and contractility.
SUN-928 Adrenal Plasmacytoma in Multiple Myeloma Patient-An Unusual Presentation
Authors: Mathew Jeena , Lubitz Sara , Zaidan Julie 
Published: May 2020

Abstract
Introduction:
Extramedullary plasmacytomas are plasma cell tumors that arise outside of the bone marrow. They are solitary lesions, and are most often located in the head and neck region, mainly in the upper aerodigestive tract. However, involvement of adrenal gland is extremely rare, with only nine case reports published to date. A mass in the adrenal gland carries a broad differential, and identification is important, as diagnosis drives treatment options. CT imaging with attenuation, timing of contrast medium washout, size, and shape, with biopsy is necessary for diagnosis of a high Hounsfield unit mass. Ruling out pheochromocytoma before biopsy of the adrenal glands is crucial.
Clinical Case:
A 64-year-old female was diagnosed with multiple myeloma after presenting with back pain and altered mental status. Imaging revealed diffuse lytic lesions in clavicles, pelvis, calvarium, long bones, ribs, and compression fractures of T8, T10, and T12 vertebral bodies. A 1.5 cm left adrenal nodule was also noted. She was treated with bortezemib, cyclophosphamide, lenalidomide, and dexamethasone, and clinically improved. Four months after initial presentation, patient was to undergo chemotherapy with melphalan and autologous stem cell transplantation. Further imaging was performed, and CT Chest revealed an enlarging left adrenal mass measuring 3.0 x 3.2 cm with increased attenuation at 37 Hounsfield units and lobulated borders with no invasion of adjacent structures. The endocrinology team was consulted for evaluation of the adrenal mass, as patient’s disease from multiple myeloma was presumed to be in remission. Differential for the adrenal mass included pheochromocytoma, primary adrenal carcinoma, and metastatic disease from multiple myeloma vs other primary. Plasma fractionated metanephrines and DHEAS were within normal range. CT guided core biopsy was performed. Cytology revealed diffuse infiltrate of atypical plasma cells. IHC studies were positive for CD138, CD56, and showed lambda light chain restriction. Cyclin D1 stain was negative, consistent with plasmacytoma. Clinically, the patient started developing progressive disease, including cutaneous plasmacytomas, and she was treated with additional chemotherapy.
Conclusion:
Adrenal plasmacytoma is extremely rare, and in a patient with multiple myeloma, should be considered in the differential diagnosis of a rapidly enlarging adrenal mass with high CT attenuation. CT guided biopsy is the definitive test for diagnosis.
References:
Li Y., Guo Y.-K., Yang Z.-G., Ma E.-S., Min P.-Q. Extramedullary plasmacytoma involving the bilateral adrenal glands on MR imaging. Korean Journal of Radiology. 2007;8(3):246–248. doi: 10.3348/kjr.2007.8.3.246.