bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT-081 Hidden in Plain Sight: Rethinking Our Approach to Allan-Herndon-Dudley Syndrome
Authors: Dye Alyssa M , Nelson Grace Bazan , Diaz-Thomas Alicia Marie
Published: May 2020

Background: Allan-Herndon-Dudley (AHD) is a rare X-linked disorder with neurological manifestations secondary to a mutation in monocarboxylate transporter 8, a protein that transports T3 into nerve cells in the brain. AHD is characterized by increased serum free T3, decreased serum free T4 and normal serum TSH levels as well as the severe neurological manifestations including global developmental delay, hypotonia, and joint contractures (1). A phase 2 trial using triodyothyroacetic acid has shown promise in treating this disorder (2). We report on three children who were diagnosed by whole exome sequencing after presenting with neurological manifestations.

Clinical Cases: Patient 1 presented at 4 months to the neurology clinic for seizures. He had a normal newborn screen. Worsening developmental delays and central hypotonia prompted a brain MRI that revealed delayed myelination for age. At 6 months a chromosomal microarray and metabolic work-up were performed and were nondiagnostic. Whole exome sequencing was obtained at the age of 4.5 years revealing a mutation in the SLC16A2 gene (p.Ser210Tyr). Thyroid studies were consistent with the diagnosis.

Patient 2 presented to neurology at 9 months for developmental delay. A brain MRI was obtained which was within normal limits. At 14 months an acylcarnitine profile was obtained which indicated a possible CPT1 deficiency, which did not fit his clinical picture. Chromosomal microarray as well as work-up for inborn errors of metabolism were performed and were nondiagnostic. Thyroid studies were obtained which showed low free T4 with normal TSH. Whole exome sequencing was obtained at the age of 2.5 years, which revealed a mutation in SLC16A2 (p.R371C).

Patient 3 presented as sibling of patient 2 with known AHD syndrome. Testing for SLC16A2 was performed at the age of 5 months and returned positive for same mutation as sibling (p.R371C).

Conclusion: Allan-Herndon-Dudley syndrome is a rare neurological disease secondary to a mutation in the T3 transporter protein to nervous tissue. A high index of suspicion as well as thyroid studies should be obtained in patients presenting with central hypotonia and global developmental delay with normal newborn screens, particularly in states that use TSH as a screening test. This is especially important as treatments are becoming available that may help prevent neurological devastation seen in these patients.

References:

1. Dumitrescu AM, Fu J, Dempsey MA, Refetoff S. MCT8-Specific Thyroid Hormone Cell-Membrane Transporter Deficiency. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993

2. Groeneweg S, Peeters RP, Moran C, et al. Effectiveness and safety of the tri-iodothyronine analogue Triac in children and adults with MCT8 deficiency: an international, single-arm, open-label, phase 2 trial. Lancet Diabetes Endocrinol. 2019;7(9):695-706.
SAT-390 Preoperative Parathyroid Ultrasound Imaging - Pitfalls and Ways to Improve Diagnostic Accuracy
Authors: Goundan Poorani , Patel Harshal , Lee Stephanie L
Published: May 2020

Introduction: Parathyroid ultrasound (US) is commonly used for pre-operative imaging to facilitate focused parathyroid surgery. It provides point-of-care imaging without ionizing radiation and is less expensive compared to nuclear scintigraphy or computed tomography (CT). Parathyroid US is, however, operator skill and experience dependent. Methods: The charts of all patient who underwent parathyroid surgery between 2016 and 2018 were reviewed. Investigators reviewed the pre-operative US images and correlated these findings with pathology reports, operative notes and with results of CT and nuclear scintigraphy imaging. The US characteristics of parathyroid lesions were described. Results: In total 146 patients underwent parathyroid surgery during the three-year study period. The average age of the cohort was 55.1 +/- 15.1 years and the male to female ratio was 1:2.6. The average pre-operative serum calcium and PTH levels were 11.6 +/- 0.9 mg/dL and 310.9 +/-305 pg/ml, respectively. 134 out of 138 patients with preoperative PTH US had images available for review by investigators. Compared to the pre-operative read that identified 106 lesions, 19 additional parathyroid lesions were identified: seven (36.8%) were easily identifiable lesions with typical US features, 3 (15.8%) were easily identifiable lesions with atypical US features, 5 (26.3%) were lesions adherent to the thyroid gland and 9 (47.4%) were small lesions that were likely only identified by the investigators due to knowledge of the final pathology and intraoperative findings. Forty-seven parathyroid lesions could not be identified by investigators and one or more of the following reasons were determined as possible explanations: lesion was small in size (14.9%), presence of a large thyroid gland (27.7%), location of the lesion deep in the neck or at an ectopic location (21.3%). The quality of stored images was inadequate in 31.9% of these cases. After review, 67.1% (compared to the actual detection rate of 61.3%) of parathyroid lesions should have been identified on preoperative US. Sixty percent of parathyroid lesions were left sided and 66.9% were inferior in location. The shapes observed were oval (48.8%), conforming (50.4%) or elongated (<1%) and echogenicity was hypoechoic (86.8%) or isoechoic (13.2%). Only a small percentage had a target sign (6.6%) or were partially cystic (7.4%). 74.8% demonstrated a feeding vessel and 33.6% had vascular arborization or scattered vascularity. Conclusions: While parathyroid lesions with typical US feature and locations are easily identified, the common reasons for failure to identify a lesion include atypical features, small size, slender configuration and adherence to the thyroid gland. Being aware of these possibilities can improve detection rate. Parathyroid lesions are also less likely to be identified when present deep in the neck or at an ectopic location outside of the neck.
SAT-510 Association of Myotonic Dystrophy with Autoimmune Endocrinopathies and Thyroid Carcinoma
Authors: Proudan Nikoletta , Gordon Murray B
Published: May 2020

Myotonic dystrophy (MD) is a multisystemic, autosomal dominant disorder associated with progressive muscle weakness, premature cataracts, frontal baldness, and cardiac disturbances. MD has been associated with several endocrinopathies including primary testicular failure, autoimmune endocrinopathies (hypothyroidism, hyperthyroidism, multinodular goiter, and Addison’s disease), thyroid carcinoma (primarily papillary), insulin resistance, and type 2 DM. Development of diabetes is thought to be related to formation of an insulin-resistant receptor because of aberrant regulation of mRNA. We describe the first reported case of a patient with MD associated with type I diabetes mellitus, Hashimoto’s thyroiditis with hypothyroidism, and follicular variant of papillary thyroid cancer. A 49-year-old female presented with acute congestive heart failure. The patient had history of type I DM diagnosed at the age of 26, complicated by mild background retinopathy, peripheral neuropathy, and nephropathy with microalbuminuria. The patient first noticed proximal muscle weakness 1 year ago that gradually progressed resulting in multiple falls. She had history of bilateral cataracts status post cataract extraction at age 26. She also had progressive dysphagia requiring PEG placement, and cognitive dysfunction with mood disorder and depression. Family history was significant for myotonic dystrophy in both maternal aunt and uncle as well as 2 cousins. EMG confirmed myotonia however genetic testing was not obtained due to cost. Due to her cognitive dysfunction and depression, she had difficult to control diabetes with HbA1c of 9.9%, and multiple previous admissions for DKA. She was status post total thyroidectomy in 2008 for follicular variant of papillary carcinoma and Hashimoto’s thyroiditis followed by I-131 therapy in 2009 and maintained on levothyroxine suppression therapy. Most recent Tg and Tg Ab were undetectable. On physical exam, the patient had a narrow, sallow face with temporal muscle atrophy, percussion myoclonus involving the thenar eminence of the hands, but no frontal balding. Work up showed LVEF of 20-24% with regional hypokinesis that led to catherization and PCI to LAD. The patient had recurrent NSTEMI which eventually resulted in CABG 1 year after presentation. The association of autoimmune endocrinopathies, thyroid carcinoma and MD suggests a possible cause and effect relationship between these disorders. In patients with diabetes and MD, previously described insulin resistance as well as cognitive dysfunction can hinder good glycemic control increasing risk for complications. Although patients with MD are typically treated by neurologists, evaluation and therapy of endocrine dysfunctions are also necessary.
MON-055 A Rare Case of a Macroadenoma Causing Cushing Syndrome in a Pediatric Patient
Authors: Patel Erica , Weigensberg Marc
Published: May 2020

Background: Pediatric Cushing Syndrome, a rare diagnosis, is almost always caused by pituitary microadenomas less than 5 mm in children older than 6 years old. We report on a 9-year-old girl with a 2.3 cm pituitary macroadenoma, whose ACTH and urinary 24-hour free cortisol were the highest recorded at our institution. Clinical Case: A 9-year-old pre-pubertal female presented with six months of frontal headaches, rapid weight gain, and hirsutism. Two months prior she developed fatigue and proximal muscle weakness and pain. On physical exam, she had plethoric round facies with acne and hirsutism, dorsal fat pad, central adiposity, and violet colored abdominal striae. Her pubertal development was tanner stage 3 for breast and 2 for pubic hair. BMI was 95th percentile and height was 40th percentile, previously 75th and 50th percentile respectively one year prior. 24 hour urinary free cortisol was 40,650 mcg/day [normal:100 mcg/day]. A 48 hour high dose dexamethasone suppression test was done as it is the most accurate in pediatric patients over 40 kg, morning cortisol was 100 mcg/dL [normal: 5-20 mcg/dL], ACTH 868 pg/ml [normal: 9-57 pg/ml], 24 Urinary Free Cortisol was 15,878 mcg/day [normal: 100 mcg/day]. A MRI Pituitary/Sella revealed a 2.3 cm pituitary macroadenoma superiorly displacing and flattening the optic chiasm, invading into the right cavernous sinus. She was referred to Neurosurgery, who did a partial transphenoidal resection, pathology consistent with ACTH producing tumor. Post-operatively she developed central diabetes insipidus and adrenal insufficiency for which she received desmopressin and oral hydrocortisone respectively. Her laboratory values eight months since surgery show normalization of ACTH and cortisol levels. The patient’s general health has improved, headaches have resolved, strength has returned, and her hirsutism is reduced. Her BMI remains elevated at 88% but is declining and growth velocity is increasing back to her pre-disease level. Conclusion: Cushing Syndrome is exceedingly rare in pediatric aged patients and pituitary macroadenomas are atypical in this population.This is a unique case of an ACTH producing macroadenoma in a Pediatric patient, which has seldom been reported in the literature, and should be considered in patients with similar presenting symptoms.
SUN-483 A Retrospective Diagnosis of Malignant Struma Ovarii After Discovery of Pulmonary Metastases
Authors: Qureshi Maham , Kishore Preeti , Boucai Laura
Published: May 2020

Background: Malignant struma ovarii is a rare ovarian tumor that is histologically identical to differentiated thyroid carcinoma.1 We present a case of a struma ovarii that was recognized as being malignant only after the discovery of pulmonary metastases.

Clinical Case: A 29 year old female presented to the hospital with acute right lower abdominal pain, suspicious for ovarian torsion. She underwent urgent right salpingoopherectomy and pathology demonstrated a mature cystic teratoma with benign struma ovarii. Two years later, a CT of the abdomen incidentally revealed bilateral pulmonary nodules. Review of the imaging showed that these pulmonary nodules were also present two years prior, and had since become larger. Video-assisted thoracoscopic surgery was performed and lung biopsy was positive for well-differentiated thyroid carcinoma. The patient then underwent total thyroidectomy which revealed a 0.3 x 0.3 cm infiltrative papillary thyroid cancer, follicular variant, without lymphovascular invasion. Thyroglobulin level decreased from 169 ng/mL pre-operatively to 80 ng/mL post-operatively, but then continued to be variable ranging from 56 to 252 ng/mL (1.6-50 ng/mL). Thyroglobulin antibodies remained negative.

Pathology from right ovary was re-reviewed at a second institution and found to be consistent with highly differentiated thyroid carcinoma with characteristic nuclear features of papillary thyroid carcinoma.

A diagnostic whole body I-131 scan showed uptake within the thyroid bed, bilateral lung nodules, left distal thigh and right mid thigh. These thigh lesions were not visualized on lower extremity ultrasound. After dosimetry was performed, the patient received radioactive iodine-131 200 mCI. Post-therapy scan six days later demonstrated uptake in the thyroid bed, bilateral lungs and bilateral thighs. About five months later, thyroglobulin level had decreased to 0.4 ng/mL with a suppressed TSH. A repeat CT chest demonstrated that the lung nodules had all decreased in size, largest from 0.5 cm to 0.3 cm.

Conclusion: Careful examination of struma ovarii pathology should be performed to evaluate for malignant features since benign appearing histology can present diagnostic difficulty.2 In this case, thyroglobulin level was lower than reported in previous cases; however, sites of metastases were responsive to radioactive iodine therapy indicating well differentiated disease and a favorable prognosis.

References: 1. Goffredo P, Sawka AM, Pura J, Adam MA, Roman SA, Sosa JA. Malignant Struma Ovarii: A Population-Level Analysis of a Large Series of 68 Patients. Thyroid. 2015:25(2): 211-216.

2. Roth LM, Miller AW, Talerman A. Typical Thyroid-Type Carcinoma Arising in Struma Ovarii: A Report of 4 Cases and Review of Literature. Int J Gynecol Pathol. 2008:27(4): 496-506.
SUN-742 Roles of Progesterone Receptor Isoform B in Non-Small Cell Lung Cancer Tumor Progression
Authors: Asavasupreechar Teeranut , Saito Ryoko , Miki Yasuhiro , Edwards Dean Paul , Boonyaratanakornkit Viroj , Sasano Hironobu
Published: May 2020

Lung cancer is a leading cause of cancer mortality worldwide. Premenopausal women often has worse survival with advanced stages of the disease compared to postmenopausal women, suggesting an involvement of sex steroids and their receptors in the progression of non-small cell lung cancer (NSCLC). Progesterone receptor (PR) was reported to be involved in an inhibition of NSCLC cell proliferation and correlated with better clinical outcome. In addition, PRB suppressed epidermal growth factor (EGF)-induced NSCLC cell proliferation and activation of ERK1/2, in the absence of progestin. However, clinical and biological significance of PRB in NSCLC patients has remained virtually unknown. Therefore, we performed immunohistochemistry using monoclonal antibody specific to the N-terminus of PRB (250H11 mAb) and 1294mAb which could detect both PRA and PRB in 124 NSCLC cases: 94 adenocarcinoma and 30 squamous cell carcinoma (SCC). Overall survival (OS) was analyzed using the Kaplan-Meier plotter (KM plotter) database, examining the correlation between the status of PRs and survival rate of the patients.

19 cases were immunohistochemically positive for PRB and 23 PRA/B positive NSCLC cases, and all of four cases harboring abundant PRs were also positive for PRB. Therefore, PRB positivity was considered to be significantly correlated with the whole PR (<0.01). Of particular interest, the abundance of PR or PRB was significantly correlated with lower tumor size in total NSCLC (p=0.0395) and SCC (p=0.023), and tended to be correlated with pleural invasion in adenocarcinoma cases (p=0.051). In addition, PRB positive cases tend to have lower tumor size than those positive with PRA/B. The analysis using KM plotter also revealed that PR was a good prognostic factor in total NSCLC patients.

Our data demonstrated that not only PR but also PRB could be a good prognostic factor and have an important role on tumor progressing in NSCLC patients. In order to further elucidate the molecular mechanisms of PRB signaling in NSCLC, we are now performing further in vitro studies. Results of our present study could contribute to the development of novel therapeutic strategies targeting PR and/or PRB in NSCLC patients.
MON-910 I’m Not Crazy! I Get a Headache When I Pee: A Case of Metastatic Bladder Paraganglioma
Authors: Sunny Sonie , Behari Gauri , Correa Ricardo , Alsayed Mahmoud , Jyothinagaram Sathya
Published: May 2020

Tumors of chromaffin cells derived from the embryonic neural crest are classified as pheochromocytomas when located in the medulla of the adrenal glands and paragangliomas when located externally to it. Bladder paragangliomas constitute less than 1% of all catecholamine-secreting neuroendocrine tumors. Usually, these tumors are functional and symptomatic, but in other cases, they can be silent. We present an interesting case of a patient with post-micturition catecholaminergic crises that went undiagnosed for several years until found to have a bladder paraganglioma.

A 60-year-old male with a past medical history of TIA, HTN, CAD, and ischemic cardiomyopathy presented with post-micturition headaches since age 14. Despite work up, no etiology was found. Eventually, the patient was referred to mental health for what was thought to be somatic symptoms. In 2010, he was diagnosed with hypertension and started keeping daily blood pressure (BP) logs, which showed BP fluctuation as high as 260s/110s with high-volume micturition, yet normotensive at other times. This led to imaging and cystoscopy which revealed a 6-cm bladder lesion. Surgical resection was completed, and pathology showed paraganglioma with positive margins and lymphovascular invasion. He was lost to follow up until 2017 when he presented with hypertensive crisis. CT and octreotide scan showed numerous osseous lytic lesions concerning for metastases. Laboratory testing confirmed excess catecholamines. He was referred to oncology, and after consideration of several treatment options, the patient was started on Xgeva and Sandostatin LAR. However, he passed away shortly thereafter.

Bladder paragangliomas are very rare and account for 6% of extra-adrenal pheochromocytomas. They occur more frequently in women than in men and clinically present mainly during the third decade of life. The patient typically suffers from hypertensive crises that may be accompanied by headache, palpitations, hot flushes, and sweating. These crises are mainly provoked by micturition, overdistention of the bladder, defecation, sexual activity, ejaculation, or bladder instrumentation. If there is high suspicion, biochemical and functional imaging workup should be performed. Surgery is the mainstay of the treatment and requires total excision. If diagnosed preoperatively, a partial cystectomy is preferred over trans-urethral resection as the majority of these tumors extend in the deep layers of the detrusor muscle. Because they are likely to recur and to metastasize, annual follow up with a measurement of plasma and urinary catecholamine levels and cystoscopy are essential. A functional imaging study (Ga-DOTATE scan) should be done to locate recurrence if symptoms reappear or catecholamine resurgence occurs.
MON-369 Calcium Gone Crazy: Recurrent Hypercalcemia in Patient with History of Hypoparathyroidism
Authors: Tarar Omer H , Rao Ambika
Published: May 2020

Introduction

Patients with post-operative hypoparathyroidism mostly require Calcium supplements and Calcitriol with goal of maintaining calcium levels in low normal range. However, calcium balance can further be dysregulated by other factors including renal failure in patients with otherwise stable levels.

We present a case of recurrent symptomatic hypercalcemia leading to multiple hospital visits in a patient with otherwise stable longstanding post-operative hypoparathyroidism that was precipitated after episode of Acute Renal Failure.

Case Presentation

71 Year old male with past medical history of Atrial fibrillation, Hypertension, Primary Hyperparathyroidism status post Parathyroidectomy (Parathyroid hyperplasia with removal of 3/12 glands) in 2003 with subsequent Hypoparathyroidism presented with lethargy and confusion few days after cardioversion attempt for atrial fibrillation. He was noted to have bradycardia and hypotension post procedure which improved subsequently. His medications included Calcitriol 0.25 mcg twice daily and Calcium Carbonate 1.25 grams twice daily. His Calcium had remained stable over the years on this regimen.

On presentation, he was found to have elevated corrected calcium of 12.5 mg/dl and Acute Renal failure with Creatinine of 8.3 mg/dl which was normal 1 week prior. He underwent hydration and subsequently required few sessions of hemodialysis with improvement in kidney function and further hemodialysis was not needed. On discharge his corrected calcium was 8.6 mg/dl and Creatinine was 3.9 mg/dl. His Calcitriol and Calcium were resumed on discharge. However, 3 weeks later he presented again with lethargy and calcium was again elevated at 14.8 mg/dl. All other workup for hypercalcemia including PTHRP, Bone marrow biopsy, Serum electrophoresis were negative. Subsequently, he had 2 more admissions for hypercalcemia and 1 admission for hypocalcemia within 1 month. Finally his calcium levels stabilized with reduced dose of Calcitriol and Calcium with close weekly monitoring initially as outpatient.

Discussion

In advancing kidney disease, the kidneys are no longer able to increase urine calcium excretion, and this removes an important safety mechanism to prevent calcium excess in patients with Chronic kidney disease. In patients with hypoparathyroidism on Calcitriol and Calcium supplements, renal failure may offset the calcium balance leading to dysregulation and erratic levels with increased tendency towards hypercalcemia.

Conclusion

Acute Renal Failure may lead to hypercalcemia in patients with otherwise stable levels. However, limited understanding of calcium balance/ regulation in renal failure, especially in setting of hypoparathyroidism further complicates the situation and may lead to difficult titration of medications.
SAT-205 POEMS: A Medical Odyssey
Authors: Havrylyan Andriy , Syed Uzma
Published: May 2020

Introduction: POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes) syndrome is a rare disorder with poorly understood pathogenesis. The incidence of endocrinopathy associated with POEMS syndrome has been recognized more frequently in the last two decades, ranging between 67-84%. The cause of endocrine dysfunction associated with the syndrome is not known, but has been described to include hypogonadism, hypothyroidism, abnormalities of glucose metabolism, hyperprolactinemia, gynecomastia in men, hyperestrogenemia, calcium abnormalities and adrenal insufficiency (AI).

Case: A 38 y/o Hispanic male was initially referred to nephrology with complaint of leg swelling. Subsequently, the patient was referred to endocrinology for abnormal thyroid function studies and ongoing fatigue. Patient had prior medical history of recently diagnosed hypothyroidism treated with levothyroxine 100 mcg daily. The most bothersome complaint was pitting edema in the lower extremities with associated pain. He also endorsed right shoulder pain exacerbated by use of the right arm. He reported unintentional weight loss of about 30 pounds in the past 2-3 years, denying night sweats. He did endorse feeling fatigued, skin darkening, and erectile dysfunction. On exam patient was afebrile, BP 120/71 mm/Hg, HR 87 bpm, no goiter, no gynecomastia, skin hyperpigmentation, darkening creases of the palms, pitting edema in lower extremities. Work up showed abnormal lambda monoclonal bands in plasma and monoclonal lambda free light chain in urine. Bone survey showed lytic lesion in right scapula. [prolactin 15.6 ng/ml (normal (NL)= 0-25), free testosterone 23.1 pg/ml (NL= 35.0-155.0), total testosterone 205 ng/dl (NL= 250-1100), LH 8.2 MIU/ml (NL= 1.2-8.6), FSH 4.3 MIU/ml (NL=1.3-19.3), TSH 17.8 uIU/ml (NL= 0.45-5.33), free T4 0.62 ng/dl (NL= 0.58-1.64), free T3 3.05 pg/ml (NL=2.5-3.9), TPO antibody (AB) negative, IGF-1 41 ng/ml (NL=53-331), AM cortisol 8.2 ug/dl (NL=6.7-22.6), ACTH 99 pg/ml (NL=6-50), aldosterone 3 ng/dl (NL ≤28), renin activity 2.78 ng/ml/h (NL=0.25-5.82), 21-hydroxylase AB negative, 17-hydroxyprogesterone 54 ng/dl (NL=42-196), DHEA-S 88 mcg/dl (NL=106-464)]. ACTH stimulation test (250 mcg) was performed with basal cortisol 8.0 ug/dl (NL= 5.0- 21.0), basal ACTH 93 pg/ml (NL=6-50), 30min cortisol 9.7 ug/dl (NL=13.0-30.0), 60min cortisol 10.2 ug/dl (NL=14.0-36.0). Pt was diagnosed with primary AI and started on hydrocortisone. CT abdomen and pelvis with contrast showed normal adrenal glands.

Discussion: Physicians should be cognizant of a unifying diagnosis in a syndrome of such a broad presentation. Endocrinopathies vary in extent of dysfunction and may fluctuate during the course of POEMS syndrome. Multidisciplinary management as well as regular reassessment of endocrine function is integral in managing this complex disease.
SAT-183 Right Adrenal Mass: An Unusual Presentation
Authors: Gondin-Hernandez Lyan , Trejo Jonathan , Sandoval Brenda , Bruder Jan M , Granda-Rodriguez Ramona
Published: May 2020

Background: Adrenal masses may be incidentally found on imaging done for other reasons. The prevalence is 4.4% and up to 10% in older patients. Malignancy is an uncommon cause in patients without a known diagnosis of cancer. The frequency of primary adrenal carcinoma in patients with adrenal incidentalomas is approximately 2.0 to 5.0%; another 0.7 to 2.5% have non-adrenal metastases to the adrenal gland.

Clinical Case: 54-year-old man with Hepatitis C, prior alcohol abuse, and cirrhosis was found to have an increase in the alpha-fetoprotein (AFP) level from normal to 244 ng/ml (nl<15.1) over a 6-month period. Liver MRI was consistent with a cirrhotic liver without focal enhancing lesions and showed a new indeterminate 7.6 cm right retroperitoneal lesion arising from the adrenal gland compared to a prior CT of the abdomen a year early. Further imaging confirmed a 9.6 x 9 x 7.6 cm heterogeneously enhancing right adrenal lesion with a necrotic center, concerning for a primary malignancy; up to 11.1cm a month later. Patient referred to Endocrine for further evaluation. There were no symptoms suggestive of Cushing’s, pheochromocytoma or primary hyperaldosteronism. On exam there were no hypertension, dorsal fat pad, supraclavicular fullness, skin thinning or purplish striae. Biochemical workup was consistent with a non-functioning adrenal mass. DHEA-S was 11 (38-313 mcg/dl). CT-guided core needle biopsy of right adrenal gland was consistent with metastatic hepatocellular carcinoma. CT pelvis with contrast re-demonstrated the right adrenal mass now measuring 11.4 x 10 x 10 cm with new enlarged retrocaval lymph node and no focal arterially enhancing lesions. During embolization of adrenal lesion/ hepatic angiogram, multiple liver lesions not previously identified were reported with the largest of 2.9cm size and enhancing lesions in the sacrum and bilateral iliac bones; decrease in size of the necrotic right adrenal mass measuring 8.2 x 9.1 x 9.1 cm 1-month post-embolization. Patient following with Oncology.

Conclusion:Unilateral isolated adrenal metastasis from occult hepatocellular carcinoma (HCC) is extremely rare. Adrenal gland is the second most common site of hematogenous spread from HCC after the lung and has been found in up to 8.4% of cases at autopsy. In our case, the adrenal metastasis was the first clinical presentation of HCC with no evident hepatic lesion until 9 months of adrenal finding; few cases have been reported. Fine needle aspiration/needle biopsy of suspected malignancy is useful to detect primary tumor in case of metastatic disease that is silent at this stage. Adrenal metastasis in HCC are seldom treated by surgery as by the time of diagnosis the tumor is usually far advanced and/or patients are poor surgical candidates. This case highlights the importance of suspecting underlying HCC in isolated adrenal mass in a patient with high risk factors.
MON-585 Racial/Ethnic Contribution and Metabolic Factors of NAFLD/NASH in the US Population: Data from NNANES III
Authors: Friedman Theodore C , Shaheen Magda , Kermah Dulcie , Pan Deyu , Schrode Katrina , Najjar Sonia Michael
Published: May 2020

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver condition. It is manifested by hepatic steatosis (HS) that can progress to non-alcoholic steatohepatitis (NASH), and even liver failure. Interestingly, it is marked by racial/ethnic disparities, with a high prevalence in Hispanics. We aimed to identify the risk factors for these chronic conditions in the US. To this end, we analyzed data from NHANES III (1988-1994) using multiple or multinomial logistic regression considering the design and sample weight. HS was identified by ultrasound. NAFLD was defined as HS in the absence of viral hepatitis or excessive use of alcohol or hepatotoxic drugs. The NAFLD population was further divided into those with NASH (defined by the HAIR score), or with simple NAFLD. The prevalence of HS was 19.8%, 16.6%, and 27.9%; of NAFLD was 17.8%, 14.7%, and 25.5%; and of NASH was 3.2%, 2.5%, and 5.1% in non-Hispanic Whites, non-Hispanic Blacks and Hispanics, respectively. Race/ethnicity was a significant predictor of HS, NAFLD and NASH, with Hispanics having the highest odds for all conditions, and non-Hispanic Blacks having the lowest odds relative to Whites (p<0.05). Other significant risk factors for all three conditions were older age, higher BMI, abnormal levels of C-peptide, and elevated serum glucose and triglycerides (p<0.05). HOMA insulin resistance was associated with HS and NAFLD (p<0.05). While smoking status was not associated with HS (p>0.05), current smokers had lower odds of NAFLD & NASH than non-smokers (p<0.05). Elevation of the liver enzyme aspartate aminotransferase was a significant risk factor of HS, while elevation of the liver enzyme alanine transaminase was a significant risk factor of NAFLD. Elevation in the levels of both liver enzymes was predictive of NASH (p<0.05). Although we included physical activity relative to national recommendation variable and the Healthy Eating Index (a measure of diet quality) in our analyses, neither of these factors was a predictor of any of the liver conditions (p>0.05). Our results showed an independent association between race/ethnicity and HS, NAFLD, and NASH, whereby Hispanics had the highest odds for every condition relative to non-Hispanic Whites. Providers should consider the race/ethnicity of their patients when evaluating the risk for NAFLD and NASH, and also be aware of the other risk factors, such as BMI and levels of C-peptide, glucose, and triglycerides.
MON-919 Primary Neuroendocrine Tumor of the Central Nervous Sistem, a Case Report and Literature Review
Authors: Louback Cybelle A , Bueno Cristina B F , Scalco Renata C , Scalissi Nilza M , Lima Jose Viana , Ricardo Gustavo P , Oliveira Marcos A C
Published: May 2020

Introduction

Neuroendocrine Neoplasms are rare, with an incidence of 5 to 100,000 inhabitants, constituting 1% of all malignancies, presenting high survival rates in general, even in metastatic diseases. However, in those poorly differentiated, as in the following case, survival is around 4% in 5 years. We will describe a case of primary neuroendocrine tumor in the brain, of which is uncommon in the literature.

Clinical case

A 26 years women was referred to the ER of Santa Casa de São Paulo, in January 2019, to be evaluated by neurosurgery, due to progressive left hemiparesis and headache for 3 months, which got worse in 4 days. On CT scan, there was a 6 x 6 cm solid-cystic, expansive, lesion in the right frontal lobe, with perilesional edema and contralateral midline 1.3cm deviation and subfalcine herniation.

Thus, the tumor was resected soon, with anatomopathological analysis showing poorly differentiated tumor of cells with scarce cytoplasm, hyperchromatic nuclei and high mitotic activity.

Immunohistochemical analysis finds 50% Ki67, with focal p53, TTF1, CD99, CD 56 and synaptophysin positivity. The main hypotheses, then, consisted of Neuroendocrine Carcinoma.

Four months after surgery, the patient reported worsening deficit, headache, pain, weight loss, being referred to the Emergency Room, once more. In RM an expansive lesion was found 6.6 x 4.4 cm, in the right frontoparietal surgical cavity, edema, compression and 0,4 cm midline deviation.

The patient was once again submitted to emergency neurosurgery, with microsurgical resection. The pathology was identical to the previous one.

We proceed with hormonal evaluation, regarding to Medular Thyroid carcinoma, Gastrinoma, Insulinoma, Pheochromocytoma, Carcinoid tumor and others.

Imaging exams were also performed to investigate other primary sites: no changes in CT scan of the chest and abdomen and PET CT FDG. However, this one showed recurrence of the intracranial lesion, with three sites of involvement, all hypermetabolic: one of 4.1 x 2.9 cm (SUV 4.9) and another of 3.9 x 3.3 cm (SUV 8, 4) in the right frontoparietal region and medial nodule to the right thalamus of 1.2 cm (SUV 6.1).

Patient currently maintain left hemiparesis, frequent pain, taking carbamazepine due to epileptic seizures, and considerable weight loss. She has an important limitation of daily activities and basic self-care, with 50% Karnofsky scale. Due to relapse, palliative radiotherapy was initiated in the region of the tumors.

Conclusion

The patient had a poor outcome in relation to cancer, with little possibility of treatment due to poor tumor differentiation and poor performance status.
SUN-301 Importance of Sexual Function Assessment in Multidimensional Evaluation of AGHD Patients: Results from the MAGHD Study
Authors: Monzani Maria Laura , Pederzoli Simone , Volpi Laura , Magnani Elisa , Diazzi Chiara , Rochira Vincenzo
Published: May 2020

Background: Adult growth hormone deficiency (AGHD) is a debilitating clinical condition leading to decreased quality of life (QoL). The impact of reduced muscle mass, weakening and loss of vitality on QoL have been well characterized in AGHD. The impact of AGHD on sexual function, a recognized factor able to modify well-being, has never been investigated. Aim: To investigate the prevalence of sexual dysfunction in AGHD patients referring to a single endocrinological center and grouped according to their history of r-hGH therapy.Methods: The Management of Adult Growth Hormone Deficiency (MAGHD) Study is a prospective, real-life trial aiming to improve management of AGHD patients through a smartphone app (MAGHD App) and a wearable device. The 83 AGHD enrolled patients (31 Females, 52 Males, mean age 56.27 + 14.68 years) were divided in 3 groups (G) according to r-hGH therapy: on long-term r-hGH therapy (G1, n=32), previously treated with r-hGH (G2, n=20), never treated (G3, n=31). Within the first phase of the study, a large database was created collecting clinical, biochemical and psychological data. In addition to QLS-H and QoL-AGHDA routinely used to assess QoL, IIEF-15 and FSFI were employed to evaluate sexual function in males and females, respectively. The nonparametric Kruskal-Wallis test was used for comparison among 3 groups.Results: Here only baseline data of the MAGHD Study are presented.According to IIEF-15 results, the prevalence of erectile dysfunction (ED) in male AGHD cohort was 60%. Erectile function (EF) score was significantly higher in G1 compared to both G2 and G3 (p < 0.05) with an ED prevalence of 35% in G1, 75% in G2 and 75% in G3. Even excluding patients with serum testosterone lower than 2 ng/ml and older than 65 years, ED prevalence did not change significantly in the 3 groups. Moreover, EF domain was inversely and directly correlated to age (R20.130, β-0.360) and IGF1 levels (R20.156, β0.395), respectively. The prevalence of female sexual dysfunction according to FSFI was 89.3%. Even though desire, arousal, lubrication and overall scores were significantly higher (better results) in G1 compared to G2 and G3 (p < 0.05), no correlation resulted between FSFI domains and IGF1 levels. Instead an inverse correlation resulted between desire domain and age.Conclusions: This study, performed in a real-life clinical setting, demonstrates a high prevalence of sexual dysfunction in AGHD patients and that r-hGH treatment seems to be associated to better sexual outcomes. These results suggest that the evaluation of sexual function should be integrated in the global assessment of AGHD patients since sexual activity is a fundamental domain able to influence both well-being and QoL.
SUN-238 Estrogen Modulates Expression Levels of Gonadotropin-Releasing Hormone Receptor (GNRHR) in Immortalized Kisspeptin Neurons in Vitro
Authors: Rayzmann Noa , Aponso Hiruni , Markgraf Christopher Y , Chappell Patrick Everett
Published: May 2020

In female animals, ovarian estradiol (E2) can act as both a negative feedback inhibitor of GnRH secretion, as well as a positive feedback stimulator at the time of ovulation. Both of these E2-regulated mechanisms work via stimulation or repression of two distinct neuronal populations of Kisspeptin (KP)-synthesizing neurons. While it is clear that AVPV KP neurons increase kiss1 expression during the preovulatory surge on proestrus, subsequent secretory mechanisms required for potentiation of GnRH surge release remain unclear. Two KP-secreting cell lines, KTaV-3, which demonstrate increased kiss1 expression under high E2 exposure, and KTaR-1, which exhibit kiss1 suppression under low E2 exposure, were used to probe the presence of GnRH receptor (GnRHR) expression under different E2 exposure conditions.

KTaV-3 and KtaR-1 cells were treated with a range of doses of E2 (5-100pM) and/or progesterone (20nM) for varying durations (4-96h), exposed to steroid hormones either constitutively or via modulating levels over time, approximating concentration changes found during the murine estrous cycle. Following RNA isolation, cDNAs were probed with primers for gnrhr. Preliminary results in KTaV-3 cells reveal the expression of gnrhr is induced only following elevated (50-100pM) E2 treatment for 18-24h. These same E2 exposure conditions were also found to increase expression of the homeobox protein dlx3, a transcription factor required for GnRHR expression in pituitary gonadotropes. In Arc-derived KTaR-1 cells, gnrhr expression was observed only following decreases in E2 concentration, while dlx3 remained constitutively elevated in this cell line. While reciprocal GnRH-Kisspeptin connections have not yet been observed in vivo, these observations suggest the potential for Kisspeptin neurons to respond to GnRH secretory changes under particular E2 exposure conditions, by modulating receptivity to GnRH at the level of the AVPV and/or Arcuate nuclei. We are continuing to explore the temporal parameters of this induction of GnRHR in KP cells, and if exposure of immortalized KP neurons to GnRH in vitro elicits expression and signaling changes in a time- and E2-dependent manner. Results will provide a more complete understanding of positive and negative feedback mechanisms required for normal neuroendocrine regulation of reproduction.
OR20-05 Regulation of Mouse Uterine Contractility by Regulator of G-Protein Signalling 2
Authors: Urrego Daniela , Wood Stephen L , Newton Robert , Slater Donna Michelle
Published: May 2020

INTRODUCTION: Uterine contractions in labour are produced by activation of receptors such as FP (PGF2α) and OXTR (oxytocin). Such receptors signal via Gαq proteins that can be selectively turned off by the regulator of G-protein signaling 2 (RGS2). RGS2 expression can be upregulated by Gαs-coupled receptor signaling. PGE2 elicits various uterine effects, some via activation of Gαs-coupled receptors. In primary human myometrial cells, PGE2 enhances RGS2 expression that attenuates subsequent oxytocin-stimulated calcium responses associated with contraction. RGS2 expression is higher in preterm non-labour versus labour human myometrium, suggesting that RGS2 promotes quiescence in the pregnant uterus. To directly study whether RGS2 dampens uterine contraction, we analyzed the ex vivo contractility of pregnant mouse uteri. We hypothesize that loss of RGS2 expression enhances oxytocin and PGF2α-stimulated uterine contractility.

METHODS: Wildtype (WT) and RGS2 knockout (KO) female mice (8-14 weeks) were time-mated and euthanized on days 15-20 of pregnancy or during active labour (n=5-11 per group). Uteri were snap frozen for RNA/protein expression analysis by qPCR and western blot. Uterine sections from d18-19 were dissected into longitudinal strips for ex vivo contractility measurement. Tissues were submerged in Krebs-Henseleit buffer and tied to force transducers to measure isometric force development. Tissues were treated with or without 1μM PGE2 for 2 hours. In parallel, pretreated and non-pretreated tissues were exposed to increasing concentrations of oxytocin or PGF2α (0.1-10uM). All tissues were treated with 100mM KCl to determine the maximum contraction at the end of the experiment. Data were analyzed by ANOVA (Bonferroni post-hoc), or Student’s t-test, as appropriate.

RESULTS: RGS2 expression in WT uteri sharply decreases at day 19 (p<0.05), remaining low during labour. OXTR and FP receptor expression increase at day 19 (p<0.01 and p<0.05, respectively) and are sustained through labour. Compared to WT, uteri from KO mice produced larger oxytocin-stimulated contractile amplitudes (p<0.05), and more frequent PGF2α-stimulated contractions (p<0.05). PGE2 pretreatment enhanced RGS2 expression in WT uteri, which reduced the peak amplitudes and integrals elicited by subsequent oxytocin treatment, compared to non-pretreated uteri (p<0.05).

CONCLUSION: RGS2 may play a pro-quiescent role in pregnancy, since RGS2 loss enhances uterine contractility. Concomitant upregulation of pro-contractile receptors and RGS2 downregulation may facilitate labour activation. This mechanisms may be involved in the etiology of spontaneous preterm labour; loss of RGS2 expression observed in human preterm labour may allow for early contractile activation. Understanding RGS2’s role in quiescence is important to developing more effective strategies for managing preterm labour.
SAT-090 Factors Affecting IGF-1 Level and Correlation with Growth Response During Growth Hormone Treatment in LGS Patients
Authors: Kim Jihyun , Kim Su Jin , Lee Jieun , Lee Young Ah , Shin Choong Ho , Seo Ji Young
Published: May 2020

Background: Primary goal of growth hormone (GH) treatment for short children is to achieve an adult height in the normal range. Different GH treatment strategies to achieve this goal include titration of GH dose according to serum insulin-like growth factor I (IGF-I) concentrations. However, IGF-I levels do not always correlate well with the growth response. The purpose of this study is to identify the factors affecting IGF-I concentration in each disease and to correct the related factors and then to identify the relationship between IGF-1 and treatment response. Methods: In this study, data of pre-pubertal children with idiopathic growth hormone deficiency (IGHD), organic GHD (OGHD), Turner syndrome (TS), small for gestational age (SGA) who were treated with recombinant human GH more than one year were obtained from the LGS Database. The LGS has been progressing since 2012 and is an open-label, multicenter, prospective, and retrospective observational study. Results: Among 2,021 registered in LGS, the subjects were 366 except for the violation of selection criteria. Among them, IGHD was 252, 16 OGHD, 31 TS, and 67 SGA. The mean age of IGHD was 6.02, and the mean bone age was 4.49 years. OGHD was 7.38, 5.74, TS was 7.13, 6.52, and SGA was 5.61, 4.96 years. The height SDS according to chronologic age was -2.76 in IGHD group, OGHD -2.33, TS -2.9, SGA -2.57. In the IGHD and SGA group, IGF-I level has a positive correlation with weight and BMI (weight; r=0.0071 in IGHD, r=0.0009 in SGA, BMI; r=0.0411 in IGHD, r=0.003 in SGA). IGF-I showed a negative correlation with chronological age in the IGHD group (r=0.0411) and mid-parental height in the SGA group (r=0.0069). There was no significant relationship between pretreatment IGF-I level and growth response. However, in the IGHD group, the growth response was significantly higher when the change in IGF-I SDS value was 1 or more (P=0.0013). Conclusion: This study is the first study using LGS data to identify factors affecting IGF-I levels in Korean children with short stature and the relationship with treatment response. IGF-I levels were positively correlated with body weight in IGHD and SGA groups. There was no significant relationship between pre-treatment IGF-I levels and post-treatment growth response. In conclusion, IGF-I concentrations should be used as a tool for treatment compliance rather than for efficacy determination.