bluuebunny/crossref_metadata_2025_split huggingface dataset:
MON-536 SPOCK1 Promotes the Progression of Papillary Thyroid Cancer ViaPI3K/Akt Signaling Activation
Authors: Li Hai , Choy Manting , Guang Hongyu , Li Yanbing 
Published: May 2020

Abstract
With the increasing incidence, thyroid cancer as one of the most common malignancy, has got widespread attention during the past few years. Papillary thyroid cancer (PTC) is the most common thyroid cancer type. Understanding the underlining molecular mechanisms of PTC is of great interest. The oncogenic role of SPARC/osteonectin, cwcv, and kazal-like domain proteoglycan 1 (SPOCK1) has been demonstrated in several cancers, however, the clinical and functional significance of SPOCK1 in PTC are largely unknown. Here, we found that the expression of SPOCK1 was upregulated in PTC tissues when comparing with the adjacent normal thyroid tissues. The overexpression of SPOCK1 was associated with the clinicopathological characteristics of the patients with PTC. We demonstrated that the proliferation of PTC cells was significantly promoted and the apoptosis of PTC cells was significantly inhibited in cells with overexpression of SPOCK1. Furthermore, we showed that knockdown of SPOCK1 arrested the cell cycle in G0/G1 phase and promoted the apoptosis in PTC cell lines. Importantly, our data suggested that SPOCK1 promoted the progression of PTC cell via regulating the PI3K/Akt signaling pathway. Taking together, our findings demonstrate that SPOCK1 enhances the activation of PI3K/Akt signaling pathway, thereby promoting the proliferation and inhibiting the apoptosis of PTC cells.
SUN-918 A Brain Metastasis in Malignant Paraganglioma Treated with Multidisciplinary Strategy
Authors: Tanabe Akiyo , Miyahara Makiko , Hashimoto Makiko , Kajio Hiroshi 
Published: May 2020

Abstract
Introduction: The most common sites of metastatic pheochromocytoma/paraganglioma (PPGL) are regional lymph nodes, bone, liver, and lung. Metastatic PPGL to the brain is very rare. Herein we describe a case of malignant paraganglioma (PGL) with a brain metastasis in the 27th year of his clinical history. Clinical Case: A 57-year-old Japanese man presented with sudden onset of headaches, speech disturbance, and mild cognitive impairment. His medical history was significant for surgery to resect a left peri-adrenal PGL at 30 years of age. At 35 years of age small lung metastases were treated with 5 cycles of chemotherapy without demonstrable response. Hypertension was diagnosed at age 44 years and diabetes mellitus at 49 years of age. The some lung metastases gradually increased in size and he underwent video-assisted thoracic surgery (VATS) at age 50 years. Plasma norepinephrine (pNE) and urine normetanephrine (uNM) levels, which were 3-fold elevated above the upper limit of the reference ranges, normalized after VATS. Subsequently, hypertension was well controlled and pNE and uNM levels remained within the reference ranges. Then, at 57-years of age, he developed central nervous symptoms and a mass with broad peritumoral edema was found in his left parietal lobe on head MRI. The 1.6 cm mass was hypervascular and isointense on T1-weighted imaging and was an inhomogeneous high-intensity in T2-weighted imaging. Both 123-I-MIBG SPECT and 18F-FDG-PET/CT imaging showed strong uptake in the brain metastasis. Although pNE and uNM levels were within their respective reference ranges, the 123-I-MIBG was diagnostic of metastatic PGL. Dexamethasone (DEX) was started to improve the brain edema. The brain metastasis was treated with linear accelerator stereotactic radiosurgery (LINAC-SRS) which was tolerated well without any adverse effects. However, the tumor volume and peritumoral edema area had not decreased one year after LINAC-SRS. Because high dose of DEX needed to continue, and his drug-induced psychiatric symptoms had worsened, we decided to move to surgical option. A craniotomy and total tumor removal was performed without any perioperative event. His condition rapidly improved and the DEX treatment was discontinued after surgery. Although he had slight hemiplegia and aphasia, and small lung metastases, he maintained a stable disease three years after surgery. Conclusion: Because PPGLs are slow growing neoplasms, multidisciplinary treatment should be considered even though there are multiple metastases. SRS has been used to treat skull base and neck PGLs with local control rates &gt;90%. However, although SRS could suppress tumor growth, dramatic tumor volume reduction is not expected. Therefore surgical approach should be considered for brain metastasis as the next strategy for intracranial decompression.
SAT-260 Resolution of a Cystic Macroprolactinoma with Dopamine Agonist Therapy
Authors: Ansari Mohammad Jamal Uddin , Abdelkarim Jumana , Baral Shailesh , Parveen Sanober , Mariam Murtaza Ali , Jabri Hadoun , Rehman Anis , Jakoby Michael G 
Published: May 2020

Abstract
Background. Prolactinomas with cystic regions occupying ≥ 50% of tumor volume are classified as cystic prolactinomas. They appear to arise from tumor necrosis or hemorrhage. Though Pituitary Society guidelines recommend surgery as first-line treatment for cystic prolactinomas, there is evidence that cystic prolactinomas are hormonally and anatomically responsive to treatment with dopamine agonists (DA). We present a case of a cystic macroprolactinoma fully responding to treatment with cabergoline. Case. A 31 year old male was referred for evaluation of gynecomastia, diminished libido, and erectile dysfunction that occurred over the course of eight months. Bilateral glandular breast tissue with a slight right asymmetry was present. Testes were 15–20 mL, soft, and without masses. Phallus and pubic hair were unremarkable. Morning (8 AM) testosterone, estradiol, and LH levels were 92 ng/dL (348–1197), 13.4 pg/mL (7.6–42.6), and 2.0 mIU/mL (1.7–8.6), respectively. Prolactin level was 331 ng/mL (4–15), and MRI with pituitary protocol revealed a 1.4 x 1.0 x 1.5 cm cystic mass with peripheral rim enhancement and extension into the suprasellar cistern. No mass effect on the optic chiasm was observed. Somatotroph, thyrotroph, and corticotroph axes were unaffected. Cystic macroprolactinoma causing hyponadotropic hypogonadism complicated by gynecomastia was diagnosed. The patient chose initial management with cabergoline 0.25 mg twice weekly. Three months after starting treatment, libido and erectile function had recovered to baseline, 8 AM testosterone was 607 ng/dL, and hyperprolactinemia was well controlled (4.2 ng/mL). At six months, anatomic resolution of the cystic macroprolactinoma was demonstrated on repeat pituitary MRI. Plastic surgery was required for management of gynecomastia. Conclusions. Surgery is recommended for management of cystic prolactinomas due to concern that a lack of dopamine receptors in the cystic components of tumors will make DA ineffective reducing tumor size. However, this case joins a growing body of evidence that DA can treat hyperprolactinemia and induce regression of cystic macroprolactinomas. For example, in a retrospective case review of patients with cystic macroprolactinomas at Massachusetts General Hospital, persistent cyst reduction occurred in 20 of 22 patients treated initially with DA, and median reduction in cyst volume exceeded 80 percent. Median time to documented cyst reduction was approximately six months, and there was no difference in degree of cyst reduction for patients treated with bromocriptine or cabergoline. The response of cystic prolactinomas to DA is similar to solid prolactinomas, and DA are reasonable initial treatment for cystic macroprolactinomas without clear indications for surgery.
MON-027 Activation of Endoplasmic Reticulum Stress Mediates Oxidative Stress-Induced Apoptosis of Granulosa Cells in Ovaries Affected by Endometrioma
Authors: Kunitomi Chisato , Harada Miyuki , Azahry Jerilee Mariam Khong 
Published: May 2020

Abstract
Endometriosis exerts detrimental effects on ovarian physiology and compromises follicular health. Granulosa cells of endometriosis patients are characterized by increased apoptosis, as well as high oxidative stress. Among several pathophysiologic factors associated with endometriosis, it is expected that oxidative stress contributes to the induction of apoptosis in granulosa cells, although the underlying mechanism remains unclear. Endoplasmic reticulum (ER) stress, a local factor closely associated with oxidative stress, has emerged as a critical regulator of ovarian function. We hypothesized that ER stress is activated by high oxidative stress in granulosa cells in ovaries with endometrioma and mediates oxidative stress-induced apoptosis. Ovaries from patients with endometrioma and control were collected to determine apoptosis, oxidative stress and ER stress by TUNEL, immunohistochemical staining of 8-OHdG and ER stress sensors, respectively. Human granulosa-lutein cells (GLCs) obtained from IVF patients were cultured with H2O2 (an oxidative stress inducer) or tauroursodeoxycholic acid (TUDCA, an ER stress inhibitor in clinical use) to assess apoptosis and ER stress by quantitative PCR and FACS. Activity of pro-apoptotic factors was determined by caspase-8 activity assay and western blotting for cleaved caspase-3. Human GLCs from patients with endometrioma expressed up to two times higher level of mRNAs associated with the unfolded protein response (UPR), including ATF4, ATF6, the spliced form of XBP1, HSPA5, and CHOP. In addition, the levels of phosphorylated ER stress sensor proteins, IRE1 and PERK, were elevated. Given that ER stress results in phosphorylation of ER stress sensor proteins and induces UPR factors, these findings indicate that these cells were under ER stress. H2O2 increased expression of UPR-associated mRNAs in cultured human GLCs, and this effect was abrogated by pre-treatment with TUDCA. Treatment with H2O2 increased apoptosis and the activity of pro-apoptotic factors caspase-8 and caspase-3, both of which were attenuated by TUDCA. Our findings suggest that activated ER stress induced by high oxidative stress in granulosa cells in ovaries with endometrioma mediates apoptosis of these cells, leading to ovarian dysfunction in endometriosis patients. Targeting ER stress with currently clinically available ER stress inhibitors, or with these agents in combination with antioxidants, may serve as a novel strategy for rescuing endometriosis-associated ovarian dysfunction.
MON-091 The Clinical and Endocrinologic Manifestations of Craniopharyngioma in Taiwanese Pediatric Population: One Medical Center Experience
Authors: Huang Ching-Chih , Lo Fu-Sung 
Published: May 2020

Abstract
Introduction: Craniopharyngioma is a rare tumor located in the suprasellar region. Due to the unique tumor location, hypothalamic-pituitary axis dysfunction is usually presented in these patients. The major symptoms are headache, visual impairment, increased intracranial pressure, and endocrinologic abnormalities. However, diagnosis is often delayed because of slow growth of the tumor and subtle symptoms. Our aims are to describe the clinical and endocrinologic manifestations before the surgical resection of craniopharyngioma in Taiwanese pediatric population. Method: We retrospectively reviewed 42 pediatric patients of craniopharyngioma in a tertiary medical center between 1996 to 2019. The clinical parameter including the initial presentation, age at diagnosis, height, weight, pituitary gland function, tumor location, time to diagnosis, and pathology reports are collected and analyzed. Results: A total of 42 patients (24 boys and 18 girls) were included in the study. The mean age at diagnosis was 8.6 years, ranging from 1 to 16-year-old. The average time to diagnosis was 7.7 months and 15.9 months for the patients with and without neurological signs, respectively. The most common initial presentation is headache (25/42, 60%), followed by visual impairment (20/42, 48%) and short stature (13/38, 34%). If short stature was the only initial presentation, 4 (4/7, 57%) of them were diagnosed of craniopharyngioma because they developed subsequent neurological deficits during clinic follow-up. Pituitary function tests showed that10 patients (10/25, 40%) had TSH deficiency and 8 patients (8/16, 50%) had central adrenal insufficiency. Image studies reported 26 patients with hypothalamic involvement and 4 patients without. All of 8 patients (8/37, 22%) with obesity had a tumor involving the hypothalamus. Pathology reports revealed 31 adamantinomatous type and only 1 papillary type. Conclusion: The study showed most (71 percent) of Taiwanese pediatric patients with craniopharyngioma presented with at least one endocrine dysfunction. Therefore, comprehensive pituitary evaluation for all patients with craniopharyngioma should be warranted. Furthermore, neurological signs and pituitary functions should both be monitored during the clinic follow-up for children with short stature or obesity in order to early diagnosis of craniopharyngioma.
MON-204 Pheochromocytoma and Paraganglioma: An Emerging Cause of Secondary Osteoporosis
Authors: Yokomoto-Umakoshi Maki , Umakoshi Hironobu , Fukumoto Tazuru , Matsuda Yayoi , Nagata Hiromi , Ogata Masatoshi , Kawate Hisaya , Miyazawa Takashi , Sakamoto Ryuichi , Ogawa Yoshihiro 
Published: May 2020

Abstract
Context: Many endocrine diseases are known to cause secondary osteoporosis, which is potentially reversible by treatment of the underlying disease itself. Pheochromocytoma (PHEO) and paraganglioma (PGL) (PHEO and PGL: PPGLs) are the rare catecholamine-producing neuroendocrine tumors, which are associated with low bone mineral density (BMD). However, PPGLs have not been recognized as a cause of secondary osteoporosis. Indeed, even the prevalence of osteoporotic fracture in patients with PPGLs is currently unknown. Furthermore, whether surgical resection contributes to the improvement of BMD has never been addressed. Objective: This study was designed to evaluate 1) whether PPGLs increase the risk of vertebral fracture (VF), which is the most common type of osteoporotic fracture and 2) whether surgical resection of PPGLs contributes to the improvement of BMD. Design and Settings: A retrospective cross-sectional study in a single referral center. Participants: Among 443 patients with adrenal tumor (AT), we included 62 patients with histologically confirmed PPGLs and 61 patients with non-functional AT. Intervention: The prevalence of VF was examined in 49 out of 62 patients with PPGLs and 61 patients with non-functional AT. In 23 out of 62 patients with PPGLs, BMD was evaluated at baseline and after surgery. Results: PPGLs had a higher prevalence of VF (43% [21/49]) than non-functional AT (16% [10/61]; p = 0.002). PPGLs were an independent risk factor for VF after adjusting for age and sex (odds ratio, 4.47; 95% confidence interval, 1.76–11.3; p = 0.001). In PPGLs, BMD expressed as Z score at the lumbar spine was significantly improved at follow-up (before -0.5±1.0, after -0.2±0.9; p = 0.005). Conclusion: This study demonstrates that PPGLs are an independent risk factor for VF and that their surgical resection contributes to the improvement of BMD in the trabecular bone. These observations support the notion that PPGLs are an emerging cause of secondary osteoporosis.
SUN-293 Acute and Long Term Evaluation of Pituitary Functions in Patients with Advanced Heart Block Requiring Pacemaker Implantation: A Pilot Study
Authors: Viswanath Arun 
Published: May 2020

Abstract
Background: Neuronal hypoxia and neuro-inflammation accompanying conditions like traumatic brain injury, stroke, cerebrovascular accidents and sub-arachnoid haemorrhage has been associated with hypopituitarism. Neuronal insults of similar magnitude and hypopituitarism [Growth Hormone (GH), gonadotropin and TSH deficiency in 27.2%, 9.0% and 2.2% patients respectively] has also been noted in a single study till date conducted in patients of ventricular arrhythmias requiring cardio-pulmonary resuscitation1. Patients with heart block, a more frequent form of cardiac arrhythmia usually presents with haemodynamic compromise and may be predisposed for developing either acute or delayed hypopituitarism which has never been studied before.
Aims and objective: Our study was aimed at exploring whether pituitary dysfunction occurs in patients presenting with heart block and requiring pacemaker implantation. We analysed anterior pituitary functions in these cohort of patients during acute hospitalization and later during follow.
Study design: Cross sectional prospective study
Materials and Methods: Fifty-one patients were included in the study (mean age-65.98±10.9years; 34 men & 17 women). Pituitary hormonal profile was done within 48 hours of presentation and after a mean follow up of 12.52 ± 2.2 months. Total T3, total T4, free T4, TSH, FSH, LH, Testosterone (in men), Estradiol (in women), Prolactin, and random Cortisol were measured in all participants at baseline and in follow-up. Fixed dose Glucagon (weight&lt;90kg-1mg; ≥90kg-1.5mg) stimulation test was done in follow-up to assess GH and cortisol axes.
Results: Among 30 (out of 50) patients who turned up for follow-up, GH, cortisol and TSH deficiency was noted in 50% (n-15), 13.3% (n-4) and 3.2% (n-1) of subjects, respectively. Pan-hypopituitarism characterised by deficiency of at least two hormonal axes was seen in 16.7% (n-5) patients.
Conclusion: Significant delayed hypopituitarism especially GH deficiency was seen among patients of heart block.
Implications: This novel finding if reproduced in subsequent studies will result in unearthing of a significant etiology of hypopituitarism which could potentially become the most common cause of acquired adult onset hypopituitarism considering the huge burden of patients with heart block. Heightened cardiovascular risk due to hypopituitarism in these patients may be reversed by active screening and replacement of deficient hormones. References: (1) Simsek, Kaya, Tanriverdi et al. (2014) Evaluation of long-term pituitary functions in patients with severe ventricular arrhythmia: a pilot study. J Endocrinol Invest 37:1057-1064Keywords: Cortisol, GH deficiency, Heart block, Hypopituitarism, Pituitary Disclosure: Authors have nothing to disclose
SAT-219 Allgrove Syndrome: How to Suspect a Problem?
Authors: Volkova Natalia , Davidenko Ilia , Dzherieva Irina , Zibarev Alexander , Ganenko Lilia , Reshetnikov Igor , Sorokina Julia , Brovkina Snezhana 
Published: May 2020

Abstract
Background: Allgrove syndrome (triple A syndrome) is a rare autosomal recessive multisystem disease characterized by adrenal insufficiency, alacrimia and achalasia. It is caused by a mutation in the AAAS gene (12q13) encoding the protein ALADIN (1). This syndrome is often associated with neurological dysfunction disorders, amyotrophy, in such cases, it is named 4A and 5A syndrome, but sometimes there is also 2A syndrome. Prevalence:&lt;1/1000000. The first description was in 1978. Clinical case: A 18-year patient A. complained of fatigue, weakness, darkening of the skin. From anamnesis of life: born from the first pregnancy without complications, weight 3200g. Parents often turned to the pediatrician with complaints: lethargy, frequent regurgitation, ARVI up to 6–7 times a year. Slow weight gain, dyspeptic syndrome (nausea, vomiting) was noted objectively. At the age of 3, the boy entered the surgical department with acute abdomen, fever, vomiting. Achalasia was revealed, reconstructive surgery was carried out. In the diagnostic search for the causes of body weight loss he was directed to the endocrinologist. There were an increase in ACTH 470 pg/ml (0,0-46 pg/ml), cortisol 0.05 µg/DL. Diagnosis: primary chronic adrenal insufficiency; the dose of hydrocortisone 10 mg/day did not change with age. An in-depth anamnesis found: the patient never cried with tears. Objectively: asthenic body type, BMI 16.5 kg/m2, hyperpigmentation of the palms, armpits; weakness in the proximal muscles of the limbs. Laboratory studies: ACTH 95 PG/ml, cortisol 0.1 µg/DL (3.7–19.4 µg/DL). The secretion of mineralocorticoids was evaluated: plasma aldosterone and renin levels were within the reference values. Ophthalmologist: injected conjunctiva, sclera. Schirmer’s test: mild alacrimia. It allowed to make the diagnosis: “Primary chronic adrenal insufficiency. Condition after surgery for achalasia (1997). Alacrimia. Allgrove Syndrome.” The dose of hydrocortisone was increased to 17.5 mg/day. In 2019, the patient complained of a sharp deterioration of health, darkening of the skin. The dose of hydrocortisone was increased to 25 mg/day (15 mg at 8.00, 10 mg in the afternoon). The ophthalmologist noted an increase in the severity of alacrimia, artificial tear drops was recommended. The diagnosis was confirmed by pathogenic mutation c.43C&gt;T of the AAAS gene. Discussion: Despite the full clinical picture, the right diagnosis was made only after 14 years. We shown the difficulty of diagnosis is due to the lack of awareness of clinicians about the disease, the importance of interdisciplinary interaction, as well as the need for follow-up of such patients. Reference: (1) Handschug K, Sperling S, Yoon SJ, et al. Triple A syndrome is caused by mutations in AAAS, a new WD-repeat protein gene. Human Molecular Genetics. 2001;10:283–290.
SAT-658 Associations of Serum and CSF Kisspeptin Levels with Metabolic and Reproductive Parameters in Men
Authors: Mutirangura Pornthira , Sitticharoon Chantacha , Chinachoti Thitima , Iamaroon Arissara , Triyasunant Namtip , Churintaraphan Malika , Keadkraichaiwat Issarawan , Maikaew Pailin 
Published: May 2020

Abstract
Action of kisspeptin in the central nervous system (CNS) is well known on reproductive regulation; however, its peripheral action is not well understood. Recent studies have shown that peripheral kisspeptin might be related to obesity and/or metabolic parameters in humans [1]; however, these associations are still inconclusive. This study aimed to 1) compare serum or cerebrospinal fluid (CSF) kisspeptin levels between different body mass index (BMI) groups 2) compare levels of kisspeptin between serum and CSF, and 3) determine correlations between serum or CSF kisspeptin levels with clinical, metabolic, and reproductive parameters. There were 40 male subjects who underwent an operation with lumbar puncture anesthesia. Subgroup analysis was performed to compare between the lean-normal group (n=13) which included lean and normal weight subjects, the overweight group (n=10), and the obese group (n=17) according to BMI. Blood samples were collected after at least 8-hour fasting before intravenous cannulation prior to the operation while CSF samples were obtained by lumbar puncture before administration of the spinal anesthesia. Serum kisspeptin and leptin levels were significantly higher in the obese group when compared to the lean-normal and overweight groups even after adjusted to age while CSF kisspeptin levels were comparable between different BMI groups (p&lt;0.05 all). Serum kisspeptin levels were significantly higher than CSF kisspeptin levels (p&lt;0.001). Serum kisspeptin was significantly positively correlated with body weight (R= 0.351), BMI (R=0.549), plasma insulin (R=0.393), and serum leptin (R=0.45) (p&lt;0.05 all), and tended to have a positive correlation with the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (R=0.29, p=0.77) but was significantly negatively correlated with plasma LH (R=-0.37) (p&lt;0.05). CSF kisspeptin was significantly positively correlated with plasma LH (R=0.452, p&lt;0.05). These results suggest that serum kisspeptin levels were related to increased obesity, leptin, insulin, and insulin resistance while CSF kisspeptin levels were related to reproductive parameters. In summary, central kisspeptin might have a role on reproductive regulation while peripheral kisspeptin might have a role on metabolic regulation. Reference: (1) Izzi-Engbeaya, C., et al., The effects of kisspeptin on beta-cell function, serum metabolites and appetite in humans. Diabetes Obes Metab, 2018. 20(12): p. 2800–2810.