bluuebunny/crossref_metadata_2025 huggingface dataset:
SUN-279 A Rare Case of Atypical Rhaboid Teratoid Tumour with Germinoma Differentiation in a 59 Year Old Woman
Authors: Pasqua Melissa-Rosina , Altoukhi Huda , Panet-Raymond Valerie , Sirhan Denis , Karamchandani Jason , Garfield Natasha , Guiot Marie-Christine
Published: May 2020

Atypical teratoid/rhabdoid tumours (ATRT) are a rare class of central nervous system malignant tumours which are comprised of elements of ectoderm and mesoderm germ-cell layers, but exhibit microscopic similarity to skeletal muscle. These tumours are more commonly seen in pediatric patients, with few case reports recently describing adult patients with this condition, in particular middle-aged women.1–3 We present the case of a previously healthy 59-year-old woman who was found incidentally to have a pituitary mass on CT head, with retrospective symptoms of headaches, polyuria, polydipsia, diplopia, and low blood pressure. At presentation, she was found biochemically to have pan-hypopituitarism with a left cranial nerve six deficit, with an MRI depicting a 19.5 x 22 x 11 mm suprasellar mass extending into the infundibulum and hypothalamus, with displacement of the optic chiasm; repeat imaging ruled out apoplexy. She was started on supplemental levothyroxine and hydrocortisone replacement therapy, and sent for urgent transsphenoidal resection, which was complicated afterwards by hypernatremia from diabetes insipidus. Preliminary reports were suggestive of germinoma given the diffuse presence of Oct 3/4 and C-kit, with a proliferation index of 99%; further cytology of lumbar puncture revealed no malignant cells. However, upon further pathological analysis, her tumour demonstrated loss of INI-1 expression, which is diagnostic of ATRT. Given the mixed features on immunohistochemistry, the final diagnosis was concluded as an atypical teratoid/rhabdoid tumour of the sella turcica with germinoma differentiation. A multi-disciplinary approach consisted of initial radiotherapy, with chemotherapy targeted towards a germinoma-type tumour, and pituitary hormone replacement including treatment for central diabetes insipidus. This represents a unique case of a rare tumour with germinoma differentiation in an older patient that has not been previously reported.

References

1.

Journal of Clinical Neuroscience 49 (2018) 16–21

2.

Acta Neurochir (Wien) (2008) 150: 491–496

3.

Surgical Neurology International 2014, 5:75
SUN-570 The Crosstalk Between Central Leptin and PPARbeta/delta Protects the Heart Against Oxidative Stress Damage and the Development of Hypertrophy
Authors: Rubio Blanca M , Mora Cristina , Mazuecos Lorena , Pintado Cristina , Arribas Carmen , Andres Antonio , Gallardo Nilda
Published: May 2020

Cardiovascular disease is a common cause of morbidity and mortality in obese people with type 2 diabetes, which is often associated with increased levels of leptin. While many studies hint at the existence of important roles for both hyperleptinemia and leptin resistance in obesity and diabetes-associated cardiovascular disease, others support that leptin has cardioprotective effects. Leptin action comprises direct effects on cardiac tissue and indirect effects mediated via the sympathetic nervous system. Since the molecular underpinnings of leptin-regulated pathways in cardiac tissue in normoleptinemic animals remain less well defined, we addressed the effects of central leptin infusion on cardiac function and remodeling analyzing FOXO1/3 and mTORC1 pathways, paying special attention to PPARβ/δ as a key leptin signal regulator. We found that central leptin regulated dynamically the network between PPARβ/δ, FOXOs, and mTORC1 in cardiac tissue, through antioxidant, thermogenic and autophagy programs. Intracerebroventricular (ICV) leptin infusion (0.2µg/day) for 7 days in male 3-months-old Wistar rats induced protection from hypertrophy without increasing TBARS and protein carbonylation nor ROS/RSN cardiac levels. These effects were further supported by both increased of Sod2 and Ucp1 expression and reduced Tnf-α. Atrophy-related ubiquitin ligase Atrogin-1, accompanied by Beclin-1 and LC3II, gene products of the autophagic pathway response, were all upregulated by central leptin. In addition, mTORC1 activity and OXPHOS protein levels were decreased without affecting cellular function. Moreover, the content of carbonylated proteins did not increase upon the central leptin treatment, suggesting a key role of leptin in preventing cardiac oxidative stress. Finally, the pharmacological inhibition of PPARβ/δ, via in vivo administration of the selective antagonist GSK0660, blunted the induction of FOXO1/3 and Atrogin-1 in the heart mediated by icv leptin infusion. Together these data support that PPARβ/δ may act as a mediator of central leptin effects on cardiac cellular reprogramming through the activation of FOXO1/3 and the inactivation of mTORC1 pathways, and the upregulation of Atrogin-1 and the genes involved in energy uncoupling.
MON-324 Management and Therapeutic Response Comparison in Prolactinomas According to Tumor Size
Authors: Flores-Cardenas Romina
Published: May 2020

Prolactinomas are the most common type of functioning pituitary adenomas and up to 50% of all adenomas in clinical practice. Prolactinomas are more prevalent in women; nonetheless, they may occur at any age and in both genders, and represent the most common cause non-physiological hyperprolactinemia. Prolactin-secreting adenomas are classified by their tumor size as follows: microprolactinomas (<1 cm), macroprolactinomas (>1cm) and giant prolactinomas (>4 cm). The clinical presentation of these tumors might differ from age, sex and size. Dopamine agonists, such as cabergoline or bromocriptine, have become the first line of treatment, since these agents decrease tumor size and prolactin (PRL) secretion. In Mexico, recent studies have focused on giant prolactinomas but there is missing data of the clinical and biochemical manifestations of the tumor size-effect within the three types of prolactinomas in our population. Objective: To determine the effect of the tumor size in the clinical and biochemical presentation, and the follow up in prolactinomas. Methods: This an observational, retrospective, retrolective study. Results: Patients were classified according to their tumor size and 489 patients with confirmed diagnosis of prolactinoma were included. The mean age was 36+-12 years old and 86% were women. The size was different among sex with 14 (2.9%) and 259 (52.9%) patients with microprolactinoma and 34 (6.9) and 152 (31.1%) with macroprolactinoma in men and women, respectively (p <0.001). The median PRL levels were higher among patients with bigger tumors, 115 (97-150) ng/mL for microprolactinomas, 219 (115-777) ng/mL for macroprolactinomas and 2000 (154-4000) ng/m for giant prolactinomas (p <0.001). Clinically, hypogonadism was more prevalent in women with bigger tumor size (p <0.001), as well as visual defects (p <0.001) and headache (p 0.008). Conclusion: The tumor size of prolactinomas affects the clinical and biochemical presentation as well as the years of follow up required.

References

1.

Lopes M.B.S. (2019). Pathology of prolactinomas: any predictive value? Pituitary doi: 10.1007/s11102-019-00997-1
SAT-378 Posterior Reversible Encephalopathy Syndrome Associated with Malignant Hypercalcemia and Hypertension Due to Primary Hyperparathyroidism
Authors: Shaamile Ferrah , Domhnall O’Halloran
Published: May 2020

Background

Posterior Reversible Encephalopathy Syndrome (PRES) is an acute neurological entity characterized by headache, altered mental status, visual loss and seizures. It can be triggered by multiple aetiologies including hypertension, eclampsia, cytotoxic and immunosuppressant drugs and, rarely, hypercalcaemia.

Case Report

A 64 years old woman presented with five weeks history of fatigue, poor appetite, dry mouth, constipation and abdominal discomfort and one-week history of nausea and vomiting. She was hypertensive at 177/88 mmHg with dry mucous membranes. Physical examination and neurological examination were unremarkable.

Laboratory investigation showed corrected calcium of 4.83 mmol/L (2.25-2.54) with

Ionized calcium of 2.62 mmol/L (1.15-1.27), parathyroid hormone (PTH) of 1330 ng/l (15-68), phosphate of 1.16 mmol/L(0.8-1.5), magnesium of 0.51 mmol/L (0.7-1.0) urea of 10.7 mmol/L (2.8-8.4), creatinine of 119 umol/L (49-90), potassium 3.4 mmol/L(3.5-5.1). She was aggressively rehydrated, commenced on Intravenous (IV) frusemide and was given IV zoledronic acid. Cinacalcet was commenced and titrated gradually up according to corrected calcium level (target corrected calcium level between 2.5-3.0 mmol/L).Electrolytes deficiencies corrected with replacement therapy.Ultrasound neck and parathyroid MIBG scan showed large 5.1cm heterogeneous lesion posterior to the right lobe of the thyroid extending inferiorly into the superior mediastinum consistent with parathyroid mass. Histology confirmed benign parathyroid adenoma.

38 hours after admission, the patient became intermittently confused and complained of visual symptoms followed by complete visual loss in the left eye. This was followed shortly by status epilepticus which required treatment with intravenous antiepileptic therapy and mechanical ventilation.Corrected calcium at that time was 3.82 mmol/L.Patient was noted to have left upper limb weakness.Computed tomography of the brain was normal and magnetic resonance imaging (MRI) of the brain showed bilateral symmetrical subcortical T2 hyper- intensities in the occipital- parietal lobes consistent with PRES.

By day five, corrected calcium was 2.52 mmol/L. On day six patient had successful parathyroidectomy. Post operatively PTH was 7.73 ng/L and corrected calcium 2.27 mmol/L. Repeated Brain MRI showed resolution of symmetrical subcortical T2 hyperintensities within both occipital lobes. She made a complete neurological recovery. DEXA scan showed osteoporosis (T score in left forearm of -3.8). She was commenced on bisphosphonate therapy.

In conclusion, we demonstrated hypercalcemia-induced PRES. This can be a life-threatening condition and can be reversed by proper treatment of hypercalcemia.
SUN-560 Simvastatin Inhibits the Pro-Inflammatory and Pro-Atherogenic Effects of Cream in Obese Subjects
Authors: Goyal Itivrita , Ghanim Husam , Hejna Jeanne , Abuaysheh Sanaa , Green Kelly , Dandona Paresh
Published: May 2020

Our previous work has shown that the ingestion of cream induces an increase in oxidative stress and other cellular and molecular indices of inflammation and atherosclerosis and that treatment with Vytorin for 6 weeks reduced and reversed majority of the effects of cream. However, it is not clear which component of Vytorin, simvastatin or ezetimibe, is responsible for these intriguing and potent effects. Therefore, we further investigated the effects of simvastatin treatment on indices of inflammation and atherosclerosis at baseline and following intake of dairy cream. Ten obese patients with LDL >100mg/dl were given simvastatin 40mg/day for 6 weeks. Subjects were asked to ingest 33ml of cream (about 300 Calories) containing about 85% saturated fat. Fasting and post-cream intake blood samples were obtained at baseline and at 6 weeks. Total cholesterol and LDLc concentrations were lowered significantly at 6 weeks following simvastatin (p<0.05). Cream intake at 0 week induced significant increases in MNC expression of IL-1β (by 58±16%), TNF-α (by 79±19%), CD16 (by 103±32%), MMP-9 (by 68±17%), TLR-4 (by 68±12%) and TLR-2 (by 53±9%) over the baselines (p<0.05 for all). Cream intake at 0 week also induced a significant increase in IL-1β plasma concentrations by 94±18% over the baseline. Simvastatin treatment suppressed fasting levels of CD68 expression in MNC (by 38±9, p<0.05) and fasting plasma levels of IL-18 and MMP-9 (by 24±11% and 28±12%, respectively, p>0.05) compared to fasting levels at 0 week. The increase in IL-1β, TNFα, CD16 and MMP-9 expression in MNC following cream intake at end of simvastatin treatment was significantly suppressed (by 41±15%, 48±17%, 87±16% and 34±8%, respectively, p<0.05) compared to that before simvastatin treatment. In addition, there was a paradoxical suppression of the expression of TLR-2 and TLR-4 (by 30±11% and 24±9%, respectively) below baseline levels following cream at 6 weeks. Simvastatin treatment also suppressed cream induced increases in plasma IL-1β concentrations by 37±11% (p<0.05, compared to increases at 0 week). We conclude that simvastatin exerts a powerful anti-inflammatory effect and reduces expression of pro-inflammatory mediators induced by cream intake. This effect is similar in nature to that observed previously with Vytorin with some differences in the magnitude of the changes.
SAT-040 Changes in Metabolic Parameters After Administration of Novel Oral Androgens with Progestational Activity for 28 Days
Authors: Yuen Fiona , Thirumalai Arthi , Swerdloff Ronald S , Liu Peter Y , Pak Youngju , Hull Laura , Page Stephanie T , Wang Christina
Published: May 2020

Background: While the metabolic effects of testosterone have been well studied, the effects of co-administration of an androgen and progestin are less established. Two novel compounds being investigated for male hormonal contraception, dimethandrolone undecanoate (DMAU) and 11β-methyl-19-nortestosterone dodecylcarbonate (11β-MNTDC), have both androgenic and progestational activity.

Aim: Characterize the effects of DMAU and 11β-MNTDC on metabolic parameters including weight, lipid parameters, insulin resistance, and adiponectin.

Methods: Two randomized, double-blind, placebo-controlled studies in healthy men were previously performed to assess the safety and tolerability of DMAU and 11β-MNTDC taken orally for 28 days. Insulin and adiponectin assays were performed on a subset of banked samples. Changes in weight, LDL-C, HDL-C, fasting glucose, HOMA-IR, and adiponectin were assessed. Two way ANOVA with post hoc Tukey HSD was performed to assess for dosage (0, 200, or 400mg) and drug (DMAU or 11β-MNTDC) effects.

Results: A total of 85 subjects were included in this secondary analysis. There was a statistically significant decrease in HDL-C (mean change -11 and -15 mg/dL) and increase in weight (3 and 2 kg) and LDL-C (18 and 23 mg/dL) in the DMAU and 11β-MNTDC 400mg groups respectively. There was no significant difference between the 200 and 400 mg groups nor differences between the two androgens. There were no statistically significant changes in fasting glucose, adiponectin or HOMA-IR.

Conclusion: There were mild changes in weight, HDL-C, and LDL-C after 28 days of DMAU and 11β-MNTDC without significant changes in markers of insulin resistance or differences between the two compounds. Changes in metabolic parameters should be monitored and considered during further development of compounds for male hormonal contraception.
SUN-179 Oncocytic Adrenocortical Carcinoma: A Case Report
Authors: Chan Jessica , Fusco Arthur A
Published: May 2020

Adrenocortical carcinoma (ACC) is a rare tumor with a poor prognosis. Oncocytic variant of adrenocortical carcinoma is considered to be an even more rare malignancy with four reported in the literature in 2002 and thirty-six documented in 2015 i ii. This case report illustrates the case of oncocytic ACC.

A 40-year-old woman post-hysterectomy from cervical cancer presented to the ER with severe left flank and back pain for two weeks. There was no weight loss or early satiety. CT scan revealed a large left adrenal mass measuring 12x9x13 cm, displacing the left kidney inferiorly with no metastasis to nearby structures. We ruled out functional adrenal mass through a 24-hour urine collection and blood work, then performed open left adrenalectomy.

Grossly, it was a large, tan-colored mass, weighing approximately 2,500 grams. On biopsy, we incidentally found the mass to be oncocytic adrenocortical carcinoma. Using the Lin-Weiss-Bisceglia criteria, it met two major and one minor criteria, when only one major criterion is required to indicate malignancy. Immunohistochemical stains showed that the tumor cells were positive for Mart-1, inhibin, and synaptophysin. Quantitative Ki-67 showed a proliferation index of 10% in average (>5% is considered malignant). Even though adrenocortical carcinoma, specifically the oncocytic variant of ACC, is a very rare occurrence, it should be on the differential diagnosis for a chief complaint of unilateral flank pain with a large adrenal mass on CT due to its poor prognosis.

Endnotes

i Hoang, M., Ayala, A. & Albores-Saavedra, J. Oncocytic Adrenocortical Carcinoma: A Morphologic, Immunohistochemical and Ultrastructural Study of Four Cases. Mod Pathol 15, 973-978 (2002) doi:10.1038/modpathol.3880638

ii Kalra S, Manikandan R, Srinivas BH. Oncocytic adrenocortical carcinoma--a rare pathological variant. BMJ Case Rep. 2015;2015:bcr2014208818. Published 2015 Apr 24. doi:10.1136/bcr-2014-208818
SAT-134 Postmenopausal Virilization: Rare Case of an Ovarian Tumor Not Easily Identified on Imaging
Authors: Jayawardena Nishanie Keshinie , Oberoi Amrinder S , Selk Karen
Published: May 2020

Introduction:

Ovarian sex cord-stromal tumors are a rare type of ovarian tumor which can be benign or malignant. Steroid cell tumors are a subtype of these tumors, representing <0.1% of all ovarian neoplasms (1). Here, we present the case of a 58 year old post-menopausal female who presented with virilization in the setting of bilateral adrenal adenomas & pelvic ultrasound without a definitive mass.

Case Report:

A 58 year old post-menopausal white female presented with deepening of voice, male pattern hair loss, increased muscle mass, weight gain, clitoromegaly, acne, increased axillary & facial hair growth. This had occurred over a period of 1.5 years. Initial investigatory labs revealed markedly elevated testosterone level of 630 ng/dL (n 2-45ng/dL). Normal FSH/LH, morning ACTH and cortisol, DHEAS, 17 OHP, androstenedione, prolactin and IGF1. Exogenous intake of testosterone was excluded. A transvaginal ultrasound showed thickened and cystic endometrial lining but no cysts or masses in the ovaries. An endometrial biopsy was normal. In the absence of a definitive source of elevated androgens, CT abdomen pelvis was done & showed remarkable for bilateral adrenal adenomas. Serum metanephrines were normal. An overnight dexamethasone suppression test was abnormal; morning cortisol level 3.1 (n 4.0-22.0). With a normal DHEAS these adenomas were considered to be the less likely etiology of her virilization. Given concern for an ovarian malignancy, a hysterectomy was recommended.

Her total testosterone level right before surgery was 954 ng/dL. Post-operatively, not only did the total testosterone levels drastically fall to 18 ng/dL merely on POD 4, but the patient reported new scalp hair growth, decreased abdominal girth & skin smoothing. Her surgical pathology was with that of a steroid tumor of the ovary.

Conclusion

Steroid cell tumors of the ovary can be benign or malignant. A prompt diagnosis is critical. In the presence of elevated testosterone levels or virilizing symptoms, an ovarian etiology must be suspected. Given the malignant potential of these tumors, if there is clinical suspicion, an expedited total hysterectomy and bilateral salpingo-oophorectomy is recommended. The objective of surgical treatment is to relieve symptoms and for staging in the case of malignancy. Timely management of the tumor can reduce metastasis and significantly improve quality of life, as seen in our case.

References

1.Kurman, R. J., Ellenson, L. H., & Ronnett, B. M. (2011). Blaustein’s pathology of the female genital tract (6th ed.). New York; London: Springer.
MON-381 Endocrinological Evaluation of Adult Thalassemia Patients
Authors: Oguz Seda Hanife , Okay Mufide , Unal Sule , Sayinalp Nilgun , Unluturk Ugur
Published: May 2020

Background: Endocrine disorders are among the most common complications in thalassemia patients. Although cardiac complications are the main cause of mortality, endocrinological disturbances have a significant impact on morbidity and quality of life. Methods: Sixty-eight patients (35 F, 33 M; 60 thalassemia major, 8 thalassemia intermedia) admitted to our outpatient clinic between August 2015 - December 2017 were included in the study. Patients were evaluated for short stature, hypogonadism, glycemic abnormalities, hypoparathyroidism, hypothyroidism and osteoporosis. Results: The average height of thalassemia major patients was 165.67±8.8 cm in men and 155.6±6.6 cm in women. Nine patients had short stature (4 F, 5 E), but 91.5% (54/59) of the whole group had low IGF-1 levels. There were 23 thalassemia major patients (11 F, 12 M) who had a history of hormonal induction therapy for delayed puberty. Overall, 60% (n = 36) of the patients were currently receiving hormone replacement therapy for central hypogonadism (19 F, 17 M). The median age at diagnosis of central hypogonadism was 22.5 years in men (IQR: 16.5-27.5) and 18 years in women (IQR: 16-25). There were five diabetic thalassemia major patients in study group whose median age at diagnosis was 20 (16-36). Of the 47 patients who underwent OGTT, 13 thalassemia major patients had prediabetes (27.7%). None of the thalassemia intermedia patients had glycemic abnormalities. Subclinical hypothyroidism was present in 19.7% (13/66) of the whole group, hypoparathyroidism was found in 8.5% (9/59) of thalassemia major patients, and vitamin D deficiency (25OH D < 20 ng/ml) was found in 70.8% (46/65) of all patients. Of 64 patients who underwent BMD, 25 had osteoporosis (39.1%) while 23 hadosteopenia (35.9%). The incidence of pathological fractures in thalassemia major patients was 20% (11/55). Conclusions: The incidence of endocrine disorders may increase in thalassemia patients due to prolonged duration of lifespan. Regular screening for newly emerging endocrinopathies during adulthood has great value. In our study, the most common endocrine disorders were vitamin D deficiency, hypogonadism, osteoporosis and glycemic abnormalities; respectively. Early diagnosis and treatment would prevent patients from having related morbidities and therefore increase quality of life.
SAT-606 Distribution of Beta Klotho Gene Expression in the Mouse Brain
Authors: Bono Bianca S , Miller Persephone A , Ly Nikita K Koziel , Chee Melissa J
Published: May 2020

Fibroblast growth factor 21 (FGF21) has emerged as a critical endocrine factor for understanding the neurobiology of obesity, such as by the regulation thermogenesis, food preference, and metabolism, as well as for neuroprotection in Alzheimer’s disease and traumatic brain injury. FGF21 is synthesized primarily by the liver and pancreas then crosses the blood brain barrier to exert its effects in the brain. However, the sites of FGF21 action in the brain is not well-defined. FGF21 action requires the activation of FGF receptor 1c as well as its obligate co-receptor beta klotho (KLB). In order to determine the sites of FGF21 action, we mapped the distribution of Klb mRNA by in situ hybridization using RNAscope technology. We labeled Klb distribution throughout the rostrocaudal axis of male wildtype mice by amplifying Klb hybridization using tyramine signal amplification and visualizing Klb hybridization using Cyanine 3 fluorescence. The resulting Klb signal appears as punctate red “dots,” and each Klb neuron may express low (1–4 dots), medium (5–9 dots), or high levels (10+ dots) of Klb hybridization. We then mapped individual Klb expressing neuron to the atlas plates provided by the Allen Brain Atlas in order to determine Klb distribution within the substructures of each brain region, which are defined by Nissl-based parcellations of cytoarchitectural boundaries. The distribution of Klb mRNA is widespread throughout the brain, and the brain regions analyzed thus far point to notable expression in the hypothalamus, amygdala, hippocampus, and the cerebral cortex. The highest expression of Klb was localized to the suprachiasmatic nucleus in the hypothalamus, which contained low and medium Klb-expressing neurons in the lateral hypothalamic area and ventromedial hypothalamic nucleus while low expressing Klb neurons were seen in the paraventricular and dorsmedial hypothalamic nucleus. Hippocampal Klb expression was limited to the dorsal region and largely restricted to the pyramidal cell layer of the dentate gyrus, CA3, CA2, and CA1 but at low levels only. In the amygdala, low and medium Klb expressing cells were seen in lateral amygdala nucleus while low levels were observed in the basolateral amygdala nucleus. Cortical Klb expression analyzed thus far included low Klb-expressing neurons in the olfactory areas, including layers 2 and 3 of piriform cortex and nucleus of the lateral olfactory tract. These findings are consistent with the known roles of FGF21 in the central regulation of energy balance, but also implicates potentially wide-ranging effects of FGF21 such as in executive functions.
SUN-914 Peptide Receptor Radionuclide Therapy for an Inoperable Small Cell Neuroendocrine Tumor in the Philippines
Authors: Alegria Rainier Mark Gabriel
Published: May 2020

Background: Peptide Receptor Radionuclide Therapy treatment for neuroendocrine tumors is a well-tolerated treatment option for patients not amenable to receiving chemotherapy and radiotherapy. Clinical Case: A 42-year-old female was evaluated by a cardiologist for complaints of new onset recurrent throat discomfort, chest pain and palpitations. Two-Dimensional echo showed a large extra-cardiac mass compressing the main pulmonary artery. Chest CT with contrast reveal a 5.8 x 6.0 x 7.2 cm enhancing lobulated anterior mediastinal mass. Attempts to excise the mass failed due to the proximity to major blood vessels. Biopsy revealed a Carcinoid Tumor that was Chromogranin A positive but was asymptomatic for carcinoid syndrome. Everolimus treatment was given but was halted due to stomatitis. The patient remained fully functional. Re-evaluation of the mass with FDG PET show an increase in tumor size. Biopsy tissue re-testing showed small cell neuroendocrine carcinoma. Urine 5-hydroxyindoleacetic acid, plasma 5-hydroxyindoleacetic acid, and serum Chromogranin A were normal. A  68Ga-DOTATATE PET/CT scan reveal a slight increase in the mass that was intensely DOTATATE-avid. Two sessions of Peptide Receptor Radionuclide Therapy (PRRT) Lutetium-177 DOTATATE given at an 8-month interval were given. SPECT/CT re-evaluation showed good response and no evidence of metastases. A  68Ga-DOTA-octreotate PET-CT scan was done and showed good response to treatment. According to treatment guidelines, small cell neuroendocrine carcinoma that are non-resectable are treated with radiotherapy plus chemotherapy. But since the patient is fully functional and has minimal symptoms, other means of treatment such as PRRT may be well suited due to good tolerability and good treatment outcomes. Conclusion: PRRT is a promising treatment for NETs that is well tolerated giving better functionality and quality of life for patients opting not to undergo chemotherapy and radiotherapy. Reference: Cadiot, G. (2019). French and European Neuroendocrine Tumor Society consensus guidelines. Annales d’Endocrinologie, 80(3), p.174.
SAT-436 Long-Term Analysis of Weight Change Following Thyroidectomy
Authors: Moore Reece , McDuffie Parker , Broadley Keri , Carneiro-Pla Denise , Javid Mahsa
Published: May 2020

Introduction: Weight gain is a common source of apprehension for patients undergoing thyroidectomy. However, contradictory reports exist regarding the presence and degree of weight gain following thyroid surgery and all known studies have short term follow-up This study evaluated weight changes following total thyroidectomy (TT) and lobectomy (L) over an extended time period. Methods: Retrospective analysis was performed of weight changes following surgery for patients who underwent TT or L (n=387) as compared with those undergoing parathyroidectomy for primary hyperparathyroidism (n=201) in a tertiary referral hospital between 2007-2012. Clinical, demographic and pre- and postoperative weight data was collected with a median follow-up of 55.6 months. Results: Postoperative weight change was observed at 1, 6, 12, and 36-months in patients who underwent TT (μ=+0.21kg, μ=+1.33kg, μ=+0.59kg, μ=+0.60kg; p<0.05) and at 6-months for patients who underwent L (μ=+0.93kg, p<0.05) compared with those who underwent parathyroidectomy. Patients having TT and L showed a general trend of weight gain compared to the control group up to 108-months post-operation; however, this weight gain was non-significant (p<0.05). Significant postoperative weight gain was observed in patients who had TT (1-month μ=+0.40kg, 6-months μ=+2.14kg, and 12-months μ=+1.40kg) and L (6-months μ=+1.04kg) for benign conditions compared with the parathyroidectomy group. Patients who had TT gained 0.40kg more than L patients at 12-months post-op (p<0.05), but no significant difference existed at other time points up to 108-months. Tukey HSD post-hoc analysis showed weight gain in benign, thyroiditis, and thyroid cancer patient groups was not significantly different from 6-months to 108-months post-operation. Furthermore, neither race nor sex was correlated with weight gain. Relative risks with 95% CI for weight gain following TT and L compared to control are: 1-month TT=1.74, 0.96-3.14, L=1.59, 0.58-2.58; 6-month TT=1.27, 0.85-1.89, L=1.42, 0.85-2.11; 12-month TT=1.44, 0.92-2.28, L=1.34, 0.86-2.36; 24-month TT=1.17, 0.82-1.67, L=1.22, 0.69-1.60. In the group of patients who gained greater than 2kg, those who underwent TT had significant weight increase compared to the parathyroidectomy group at 6-months postoperatively (Mann-Whitney U, p=0.011). In the subgroup of patients with weight gain greater than 2kg, those who had L did not have significant weight increase at any time point. Conclusion: Weight change following TT when compared with parathyroidectomy is significant shortly after surgery. However, these changes are not significant at long-term follow-up.
SAT-069 Advantages of Next Generation Sequencing (NGS) in Hypophosphatemic Disorders Diagnosis. First Case of SLC9A3R1 Gene Pathogenic Variant Detected in a Pediatric Patient
Authors: Ramirez, Biochemist Pablo , Palma Isabel Di , Viterbo Gisela , Perez-Garrido, Biochemist Natalia Isabel , Pujana, Biochemist Matias , Juanes Matias , Belgorosky Alicia , Marino Roxana Marcela
Published: May 2020

Background: Hereditary hypophosphatemic rickets (HHR) is a group of inherited disorders characterized by hypophosphatemia due to renal-phosphate wasting and impairment of vitamin D metabolism, rickets and disproportioned short stature. Different genetic defects are known to cause HHR, but similar clinical and biochemical features were reported. Dominant-X-linked HR (XLHR) is the most frequent form, with an incidence of 1 in 20.000, although dominant and recessive autosomal forms are also described. XLHR is caused by inactivating mutations in the PHEX gene (located at Xp22.1), encoding a endopeptidase which regulates the phosphaturic secretion. Affected individuals present with a broad phenotypic spectrum, ranging from isolated hypophosphatemia up to severe symptoms of rickets. Therefore NGS studies represent an useful tool for molecular diagnosis characterization Aim: to develop a reliable NGS diagnostic tool for HHR and related disorders.

Patients and Methods: we develop a NGS panel including 13 genes related with HHR or other hypophosphatemic disorders, using Illumina TruSeq Custom Amplicon technology.

We analyzed 12 patients which have been sent to our laboratory for molecular genetic testing under suspicion of HHR based on clinical phenotype and laboratory studies but with no proven mutation in PHEX gene by Sanger sequencing or MLPA analysis or other hypophosphatemic disorder.

Results: A previously reported pathogenic variant (p.Arg153Gln) was found in SLC9A3R1 gene encoding NHERF1cotransporter, which interact with phosphate and sodium renal transporter NaPi2a in a 13 months old girl. There are only 5 reported cases with alterations in this gene and all of them were adult patients with nephrolithiasis. The patient was referred to our hospital due to hypercalcemia. She had poor weight gain and laboratory findings showed high serum calcium (16,6 mg/dl), mild serum phosphate (3.9 mg/dl), very low parathyroid hormone (PTH) (< 3 ng/ml), normal 25OHvit D (40 ng/ml) levels, and elevated urinary calcium/ creatinine rate (2), and low phosphate tubular reabsorption (85%). Ultrasound showed nephrolithiasis. Since she had hypophosphatemia and renal phosphate wasting with symptomatic severe PTH independent hypercalcemia probably secondary to excessive calcitriol production with hypercalciuria, a molecular alteration of CYP24A1 or SLC34A1genes was suspected.

Conclusion: NGS allowed to report for the first time the identification of a mutation in the SLC9A3R1 gene in a pediatric patient. An early diagnosis might improve long term outcome starting the right therapy to avoid progression of nephrolithiasis and nephrocalcinosis and chronic renal failure.
MON-526 Comparison of ACR-TIRADS to American Thyroid Association Guidelines: Can We Choose Wisely Without Missing Malignancy?
Authors: Halperin Ilana Jaye , Qiang Judy
Published: May 2020

Thyroid ultrasound has been widely used to determine which nodules need further work up. The goal of this study was to apply the new ACR-TIRADs criteria to a retrospective data set and compare the outcomes to the ATA scoring system. Methods: In a retrospective study, ultrasonographic images of the all nodules biopsied in 2015 were reviewed by radiologists, blinded to fine needle aspiration (FNA) biopsy result, using a checklist to report the image. The checklist was prepared based on 2015 ATA guideline. The ultrasonographic characteristics of thyroid nodules were compared with the result of biopsy to determine positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity of checklist in predicting malignancy. These results were published previously. The same data was then reviewed using the ACR-TiRADS tool to assess the number of US and FNA that would been avoided and the number of non-benign cytologies that would have been avoided had these criteria guided care in 2015. Results: 419 thyroid nodules were reviewed 7.1% were malignant, 10.3% were FLUS and 78.3% were benign. Sensitivity of the ACR-TIRADs and ATA respectively was to detect non-benign nodules was 70% and 97% Specificity was 29% and 11%. Positive predictive value was 18% and 9% whereas Negative predictive value was 81% and 98%. 28% of the FNAs done in 2015 could have been avoiding if applying the TIRADs criteria, however 15 non-benign and 8 malignant cases would have been missed.Conclusion: The TIRADs approach adds value to the system by reducing many unnecessary biopsies but clinicians need to use their own judgement as some non-benign cases will be missed.
SUN-585 Associations Between UCP1(rs1800592),UCP2(rs6593366) and UCP3(rs1800849) with Fasting Glucose, Body Mass Index, and Energy Expenditure
Authors: Figueroa-Vega Nicté , Perez-Luque Elva L , Malacara Juan M
Published: May 2020

Background: The uncoupling proteins (UCPs) belong to the mitochondrial inner membrane anion carrier superfamily and play an important role in energy homeostasis. UCP-1 is expressed mostly in brown adipose tissue (BAT) and act in the thermogenesis and regulation of energy expenditure. UCP-2 has a role in the metabolism of fatty acids direct and indirectly path insulin secretion. UCP-3 is specific of skeletal muscle and BAT and may affects the adaptive and translocation of fatty acids. Genetic polymorphisms in these proteins have been associated with obesity, as rs1800592 (-3826 A/G) in UCP-1 gene. The rs659366 (-866GA) UCP-2 has being associated with high expression of its RNAm, decrease of obesity risk, and increase of energy expenditure. The rs1800849 (-55CT) UCP-3 has been associated with low risk of type 2 Diabetes Mellitus, but its association with body mass index is controversial. Objective: To analyze the association of the polymorphisms rs1800592 UCP-1, rs659366 UCP-2, and rs1800849 UCP-3 with BMI and resting energy expenditure (REE). Material and Methods: We included 120 subjects with BMI>30kg/m2 and 100 subjects with BMI between18.5 -24.9 kg/m2, aged 20 to 50 years. Anthropometric data were recorded and the REE was measure for indirect calorimetric. Fasting glucose and lipid profile were assessed. Leptin, insulin and acylated-ghrelin were quantified by ELISA. Genomic DNA was extracted using comercial kit. Genotyping for three polymorphisms was performed by allelic discrimination using Taqman probes. Results: All the three polymorphisms of UCPs showed distribution in accordance with Hardy-Weinberg equilibrium. The weight, BMI, glucose, triglycerides, leptin, insulin, HOMA-IR, and REE levels were signitifcantly higher in obese subjects. There was a strong correlation between REE with BMI (r=0.42, p<0.00001) and with insulin levels (r=0.229, p=0.001) in all group. No differences in genotypic and allelic frequencies of rs1800592 UCP-1, rs659366 UCP-2 and rs180084 UCP-3 polymorphisms between obese and lean subjects. No differences among the genotypes rs1800592 UCP-1 and rs1800849 UCP-3 with metabolic variables. In rs659366 UCP-2 polymorhism, the REE and glucose concentrations were lower in carriers of rs659366AA genotype (F=3.11, p=0.046; F=2.97, p=0.053, respectively) in whole group. In obese subjects with rs659366AA UCP-2 genotype, the REE was significantly low (F=4.15, P=0.017). Conclusion. In this work the obese subjects with rs659366AA genotype had low REE. We found low glucose concentrations in the carries of rs659366 AA genotype.
SAT-LB128 A Case of Metformin Associated Lactic Acidosis and the Importance of Medication Reconciliation in End-Stage Renal Disease
Authors: Tsai Karen , Ning Weihuang Vivian , Barnett Braden , Lin Eugene
Published: May 2020

Background: Metformin is commonly used in the treatment of diabetes mellitus due to its low cost, ease of administration and titration, and favorable side effect profile as it does not cause weight gain and rarely causes overt hypoglycemia. An important yet rare side effect of metformin use is metformin associated lactic acidosis (MALA) which can be seen in patients with significant renal impairment and is associated with high mortality.

Clinical Case: We present a 54-year-old man with hypertension, type 2 diabetes mellitus, and recently diagnosed end-stage renal disease (ESRD) on hemodialysis who presented with shortness of breath and syncope and found to have an elevated lactate to 40.5 mmol/L (reference range: 0.5-2 mmol/L). Notably, the patient was admitted at an outside hospital two and a half weeks prior for a new diagnosis of ESRD and initiated on hemodialysis three times a week. At the time of discharge from his prior hospitalization, he was instructed to continue his diabetes medications: metformin 1g twice a day, glipizide 10 mg twice a day, and pioglitazone 30 mg daily. The patient was admitted to the intensive care unit and found to have MALA. Nephrology was consulted and the patient clinically improved with hemodialysis. Within six hours of presentation, the patient’s clinical course rapidly improved with complete resolution of lactic acidosis and hemodynamic instability within 48 hours.

Conclusion: Although metformin is the most commonly used drug in diabetes mellitus, the side effect of metformin associated lactic acidosis is rarely seen in the inpatient setting. Patients with ESRD are at high risk for complications resulting from poor medication management. However, because metformin is primarily renally cleared, it should be discontinued in those with significant renal impairment. With increased awareness and understanding of MALA, providers can prevent MALA by appropriately stopping or dose reducing metformin in patients with chronic kidney disease. Educating patients on their medications—including their uses, side effects, and drug-drug and drug-food interactions—could help reduce the aforementioned medication-related problems. Clinicians should have a high suspicion of metformin associated lactic acidosis in any patient presenting with multi-organ failure due to its variable clinical presentation. If MALA is suspected, providers should consult nephrology so that patients can be started on hemodialysis.
SAT-LB69 Severe Disabling Musculoskeletal Pain as a Side Effect of Bisphosphonates: A Case Report and Review of Literature
Authors: Bawal Dionise Ysabelle Vellon , Gomez Maria Honolina Sero
Published: May 2020

We report a case of a 57-year-old woman who developed severe musculoskeletal pain after taking one dose of Alendronate 70mg for treatment of osteoporosis. The pain was so debilitating that the patient was unable to sit up, stand, or move without assistance, and any kind of movement aggravated the pain.

Key words: bisphosphonate, severe muscle pain, case report, osteoporosis

Methods

A detailed case report is presented. A review of the current literature on the side effects of bisphosphonates was made for reference.

Results

Development of severe, disabling musculoskeletal pain was noted after taking one dose of Alendronate 70 mg tablet. The pain was severe enough to hinder the patient from sitting or standing up, and any form of movement seemed to worsen the pain. Discontinuation of the drug, pain relievers and complete bed rest afforded slight relief of symptoms. Complete resolution of pain only occurred after 72 hours. Review of literature showed that muscle pain with intake of bisphosphonates occurred in a few patients, and were mostly found in case reports or case series. Other commonly associated side effects with bisphosphonate therapy were also briefly discussed.

Conclusion

The case presented emphasizes that bisphosphonate therapy, although frequently used uneventfullyn, may still produce adverse effects in a few patients. A handful may present with severe debilitating muscle pain as seen in our patient. Literature review showed that another subset of patients may react differently and present with cardiac or ocular symptoms. What must be taken from this paper is the importance of patient education regarding these possible adverse events that although infrequent, may still happen. These unpleasant adverse effects may greatly affect compliance and ultimately have a bigger impact in the fight against osteoporosis.
SUN-LB65 Circulating Micrornas Linked to Bone Metabolism Are Affected by Sequential Anti Osteoporotic Treatment in Postmenopausal Osteoporosis
Authors: Yavropoulou Maria , Makras Polyzois , Anastasilakis Athanasios , Papatheodorou Athanasios , Rauner Martina , Hofbauer Lorenz C , Tsourdi Elena
Published: May 2020

Depending on osteoporosis severity a long-term treatment, often in the form of a sequential regimen, may be required. The expression of microRNAs (miRs) related to bone metabolism in the serum is potentially affected by anti-osteoporotic treatment. Here, we investigated the effect of sequential treatments on microRNA expression profile in the serum.

Methods: This is an observational, open label, non-randomized clinical trial that included 37 postmenopausal women with osteoporosis who were treated with denosumab (Dmab) for 1 year. Patients had been previously treated for 2 years with either teriparatide (n=20), or zolendronate (n=6), or were treatment-naïve (n=11). We evaluated changes in the relative serum expression of selected miRs linked to bone metabolism at 3 and 12 months of Dmab treatment at each group separately.

Results: In the group of patients who were previously treated with teriparatide, the relative expressions of miR-21a-5p, miR-29a, and miR-2861 were significantly decreased at both 3 months (fold change 0.13, p<0.001 for miR-21a-5p; fold change 0.68, p=0.044 for miR-29a; fold change 0.16, p<.0001 for miR-2861), and 12 months (fold change 0.09, p<0.001 for miR-21a-5p; fold change 0.65, p=0.044 for miR-29a; fold change 0.19, p<0.001 for miR-2861) of Dmab treatment. The relative expression of miR-23a-3p was also significantly decreased (fold change 0.65, p<0.001) at 12 months of Dmab treatment. The relative expression of miRs was not changed among patients previously treated with zolendronate. No change was also observed during Dmab treatment in previously treatment-naïve osteoporotic women.

Conclusions: The expression of circulatings miRs linked to bone metabolism during Dmab treatment is depended on previous treatment status. Patients previously on teriparatide treatment present alterations of the relative expression of miRs related to the expression of key osteoblastic genes such as RUNX-2 (miR-23), collagen type 1 (miR-29a) and HDAC5 gene (miR-2861) during subsequent treatment with Dmab Our data suggest that teriparatide may influence the subsequent anti-resorptive effect of Dmab on bone metabolism at post-transcriptional level.
SUN-LB83 Outpatient Radiofrequency Ablation Is a Safe and Effective Treatment Option for Benign Thyroid Nodules in North America
Authors: Aljammal Jules , Ahmad Shahzad , Hussain Iram
Published: May 2020

Background: Radiofrequency ablation (RFA) of thyroid nodules is a non-mainstream treatment option for benign thyroid nodules. Studies in Asia and Europe (1) have demonstrated RFA to be an effective outpatient alternative to surgery, however, these results have not been reproduced in North America. Hypothesis: RFA of symptomatic benign thyroid nodules can reduce morbidity associated with thyroidectomies, without sacrificing favorable clinical outcomes. Methodology: A retrospective review of 11 patients (all female and Caucasian) with 13 thyroid nodules treated with RFA in our practice was conducted (Nov 2018 - Oct 2019). The 9 nontoxic nodules were biopsied twice, and 4 toxic adenomas were biopsied once; all had benign cytopathology results prior to RFA. RFA was done under local anesthesia/conscious sedation, with follow-up telephone call after 2 days to assess complications (pain, voice change, hematoma/swelling, skin burns). Nodule volume in mL (length x depth x width in cm x 0.525), cosmetic score (2), and thyroid function tests (TSH and free T4) were recorded pre-procedure, and 6 - 10 weeks post procedure. The volume reduction rate (VRR) was calculated as follows: [(baseline volume - final volume)/baseline volume] x 100 (%). Results: The mean age of the patients was 45 years; 7 were euthyroid (not on thyroid hormone replacement), and 4 had hyperthyroidism. The mean volume of treated thyroid nodules decreased from 12.3 cc to 5.6 cc, with a mean VRR of ~ 54%. Thyroid nodules with volumes less than 10 cc (smaller) had a VRR of ~ 75%, whereas nodules with volumes more than 10 cc (larger) had a VRR of ~ 50%. The VRR between smaller and larger nodules (p-value: 0.11), and toxic adenomas and nontoxic thyroid nodules (p-value: 0.26), was not significantly different. 3 out of 4 patients with toxic adenomas normalized their TSH levels; 1 patient normalized free T4 levels, but TSH remained suppressed. None of the patients developed hypothyroidism. The cosmetic scores (indicating visible or palpable mass) improved by 50%. All patients had complete resolution of compressive symptoms. Minimal discomfort only reported at time of procedure. No complications were reported at the 2-day, or the 6-10-week follow-up. Conclusions: Outpatient RFA is a safe and effective treatment for benign thyroid nodules and toxic adenomas. There were no complications in our study, however, this may be limited by the small sample size and relatively short follow-up duration. Advantages of RFA include avoiding lifelong thyroid hormone replacement and complications of surgery and/or general anesthesia. We propose that RFA be considered as a first-line therapy for the treatment of benign thyroid nodules for these reasons. References: (1) Feldkamp, et al. Exp Clin Endocrinol Diabetes. 2020 Jan 7. doi: 10.1055/a-1075-2025. (2) Dobnig, et al. Thyroid. 2018 Apr;28(4):472-480. doi: 10.1089/thy.2017.0547.