bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT-259 Acromegaly by Pituitary Adenoma Associated with ACTH-Independent Cushing Syndrome by Adrenal Carcinoma: Case Report
Authors: Minuzzi Ricardo Kunde , Landenberger Giullia Menuci , Pereira Lima Julia Fernanda Semmelmann , Oliveira Miriam da Costa , Leães Rech Carolina Garcia Soares 
Published: May 2020

Abstract
Introduction: The coexistence of acromegaly and Cushing’s syndrome is quite rare. Case reports with this association have been described in the literature, including both ACTH-dependent and ACTH-independent Cushing’s syndrome. In these cases, when considering ACTH-independent hypercortisolism, the main etiology reported is adrenal adenoma. We will describe the case of an acromegalic patient with ACTH-independent cushing syndrome due to adrenal cortical carcinoma.
Clinical Case: A 62-year-old male patient with acromegaly diagnosed by headache investigation. He had a previous medical history of T2DM for 20 years, grade III obesity (BMI 40.3), hypertension, obstructive sleep apnea and depression. Initial investigation showed IGF-1 levels of 818 ng/mL (81–225), GH: 3.39 ng/mL (&lt;0.97), prolactin diluted: 2.578 ng/mL (2.1–17, 7), LH: &lt;0.07 mIU/mL (1.5–9.3), FSH: 0.6 mIU/mL (1.4–18.1), total Testosterone: 51 ng/dL (241- 827) Cortisol at 8 AM: 15 µg/dL, TSH: 1.54 µg/dL (0.55–4.78), free T4: 1.0 ng/dL (0.89–1.76) and brain MRI with a large expansive sella turcica process, invading the right cavernous sinus, with growth to the sphenoid sinus and suprasellar compressing the optic chiasm, suggestive of pituitary macroadenoma. He underwent transsphenoidal resection with histology confirming a prolactin and GH co-secretory pituitary adenoma with Ki-67: 5%. He started treatment with octreotide LAR (30 mg/month) and cabergoline (3.5 mg/week) and underwent 25 radiotherapy sessions. Three years after the diagnosis of acromegaly, the patient underwent CT scan of the abdomen, which identified a 3.8 cm left adrenal nodular lesion that evolved in the 12-month control exam to nodular image with lobulated contours (5.0 x 3.4 cm) and non-contrast phase density &gt; 25 HU. At that time, he had two 24-hour cortisoluria samples: 640.9 and 637 µg/24hs (54–403) and ACTH &lt;5.0 pg/mL (&lt;46).The patient underwent videolaparoscopic adrenalectomy confirming the pathology of the lesion compatible with adrenal cortical carcinoma with invasion of the capsule and peri-adrenal adipose tissue and Ki-67: 20%. Even after primary resection of the adrenal lesion, the patient evolves with local and metastatic progression of the disease, dying a few months later, due to infectious complications of a new surgical approach.
Conclusions: To the best of our knowledge, this is the first case of ACTH-independent Cushing’s syndrome caused by adrenocortical carcinoma in an acromegalic patient.
SAT-677 A Case of Opdivo Induced Type 1 Diabetes
Authors: Lucier Jessica , Tabatabai Laila 
Published: May 2020

Abstract
BACKGROUND: Opdivo, or Nivolumab is an immunotherapy medication that works as a checkpoint inhibitor. It is used in various cancers not amenable to surgery, including lung cancer and metastatic melanoma. Opdivo has proven to be a beneficial treatment, though it is not without complications including thyroid dysfunction, hypophysitis, and autoimmune induced diabetes.
Clinical Case: An 80 year old female with a PMH of type 2 diabetes mellitus, hypertension, hyperlipidemia, and melanoma with metastasis to the bone was evaluated by endocrinology for acute worsening of her type 2 diabetes. The patient had been diagnosed with diabetes 10 years prior. She was well controlled on 22 units of levemir and Janumet. Her baseline HbA1c was 6.7%. She had no known complications from her diabetes. Four months prior to presentation she had been started on monthly Opdivo infusions for her metastatic melanoma, which she was tolerating well.
On presentation to the hospital, she had persistent hyperglycemia in the high 400’s, an elevated anion gap, and an elevated betahydroxybutyrate. She had no signs of acute infection and no significant changes in her diet or activity level. She was started on an insulin drip for diabetic ketoacidosis until her anion gap resolved. At discharge she was continued on 22 units of levemir, a humalog sliding scale, and Janumet. At that time it was unclear what precipitated her acute change in glycemic control.
At her follow up endocrinology appointment several labs were drawn including a c-peptide, though antibodies were not obtained. Her c-peptide was less than 0.1 with a concurrent blood glucose value of 370. It was determined that she had developed autoimmune induced diabetes secondary to Opdivo therapy and would require life long insulin therapy. Her Janumet was discontinued. She was started on a T-slim insulin pump and Dexcom G6 sensor, with improvement in her glucose control. Her Opdivo treatments were discontinued. She has since developed worsening metastasis in her femur and will be started on Yervoy. Yervoy also carries a risk of further endocrine disorders, including increased risk of hypophysitis.
Discussion: Acute changes in glycemic control warrants further investigation to determine the underlying precipitating factor. The most common complications of Opdivo are rashes and fatigue, though endocrinopathies have been noted in several patients. It was crucial in this patient to identify this side effect of Opdivo, as it helped to prevent further episodes of DKA. Careful review of recent medication changes helped identify this uncommon complication of Opdivo and prompted a timely change in her diabetes care regimen.
SAT-541 Difference in Aldosterone Dependency Between Cardiovascular Diseases and Renal Impairments in Patients with Primary Aldosteronism
Authors: Sone Masakatsu , Ohno Youichi , Kawashima Akiyuki , Inagaki Nobuya , Naruse Mitsuhide ,   JPAS/JRAS Study Group
Published: May 2020

Abstract
BACKGROUND:
There have been several clinical studies examining the factors associated with cardiovascular disease (CVD) and renal impairment in patients with primary aldosteronism (PA); however, their results have left it unclear as to whether they are affected by the plasma aldosterone concentration (PAC) itself.
Method:
This is a retrospective cross-sectional study. We assessed the PA database established by the multicenter JPAS (Japan Primary Aldosteronism Study) and compared the prevalences of CVD (stroke, ischemic heart disease, and heart failure) and renal impairment (proteinuria and lowered eGFR) among patients with PA and those with essential hypertension (EHT). We also performed logistic regression analysis to determine which parameters significantly increased the odds ratio for these complications.
Results:
The prevalence of CVD was significantly higher among 2814 patients with PA than among matched patients with EHT. The prevalence of proteinuria was also significantly higher among PA than EHT patients, whereas there was no significant difference in the prevalence of lowered eGFR. Multivariable logistic regression analysis showed that the PAC significantly increases the adjusted odds ratios for proteinuria and lowered eGFR independent of other known risk factors. By contrast, the PAC was not linearly related to the adjusted odds ratio for CVD.
Conclusion:
Plasma aldosterone levels are closely associated with renal impairment in patients with PA. This is contrast to our finding that the PAC was not, itself, linearly associated with CVDs, such as stroke or ischemic heart disease. The mechanism underlying the kidney damage in patients with PA may thus differ from that affecting the cardiovascular system.
SAT-576 Possible Involvement of Thyroid Function in PCSK9 Inhibitor Therapy
Authors: Iwabuchi Masayasu 
Published: May 2020

Abstract
INTRODUCTION
Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibition is an effective strategy for lowering plasma LDL-cholesterol and enhancing the LDL-cholesterol lowering ability of statins. PCSK9, a serine protease that binds to the LDL receptor promoting its degradation, is an important regulator of LDL metabolism. In addition, LDL-cholesterol is also controlled by TSH and thyroid hormones via PCSK9. TSH has received increasing attention as being closely associated with increased LDL-cholesterol level and higher atherosclerotic risks. In vitro study, the effects of TSH on hepatic PCSK9 expression in HepG2 cells were reported (1). I here report a case of transient hyperthyroidism secondary to PCSK9 inhibitor therapy. This case highlights the involvement of thyroid function in PCSK9 Inhibitor therapy.
CLINICAL CASE
A 65-year-old man had a weight loss of 6 kg (13 lbs.) in 4 months, accompanied with fatigue. He had a past history of myocardial infarction and his LDL was 83 mg/dL by 2.5mg of rosuvastatin and heart rate was controlled by 10mg of carvedilol. Six months ago, he started a PCSK9 Inhibitor therapy with 140mg of evolocumab every 2 weeks for 6 weeks. He had no preceding viral illness and denied anterior neck pain or tenderness. His height was 1.53 m, weight 52.6 kg (115 lbs.), and body mass index (BMI) 22.46 kg/m2. His thyroid was not enlarged and non-tender without clear palpable thyroid nodules or neck lymph nodes. Hyperthyroidism was suspected and confirmed by thyroid function tests: TSH was less than 0.0005 μIU/mL (normal 0.35–4.94), and free T4 1.830 ng/dL (0.70–1.48). Graves’ disease was considered, and thyroid antibody tests performed. Thyroid peroxidase (TPO) antibody titer was less than 9 IU/mL (&lt;9), and TSI 141% (&lt;120%). To confirm the diagnosis of this hyperthyroid patient, Technetium-99m uptake and scan was done which showed uptake of 0.8% (0.5–7%). After careful observation for 2 months with 5mg of carvedilol, he turned asymptomatic and free T4 lowered to 1.480 ng/dL and TSH remained less than 0.0005 μIU/mL.
CLINICAL LESSONS
I here report a case of transient hyperthyroidism secondary to PCSK9 inhibitor therapy. There has been no report of hyperthyroidism induced by PCSK9 inhibitors. Immunological influence of anti-PCSK9 therapy on thyroid is unknown. In this case, the decrease of TSH due to hyperthyroidism was considered to reduce hepatic PCSK9 expression, leading to additive effect to PCSK9 inhibitor. PCSK9 inhibitors may modify the effects of hyperlipidemia treatment by causing changes in thyroid function. When using PCSK9 inhibitors, follow-up of thyroid function should be considered. This case highlights the involvement of thyroid function in PCSK9 inhibitor therapy.
Reference
(1) Gong, Y., Ma, Y., et al. Thyroid stimulating hormone exhibits the impact on LDLR/LDL-c via up-regulating hepatic PCSK9 expression. Metabolism. 2017;76;32–41
OR20-01 AMH Preserves Fertility in Chemotherapy-Treated Mice Through a Mechanism Involving Autophagy
Authors: Beau Isabelle , Sonigo Charlotte , Binart Nadine 
Published: May 2020

Abstract
Chemotherapy-induced ovarian failure and infertility is an important concern in female cancer patients. The follicular ovarian reserve is established early in life then keeps declining regularly along reproductive life. This reserve is constituted by dormant primordial follicles (PMF) which are necessary to maintain female reproductive function. There is a continuous repression of PMF activation in early growing follicle through the balance between factors activating the initiation of follicular growth, mainly actors of the phosphatidyl-inositol-3-kinase (PI3K) signaling pathway, and inhibiting factors such as Anti-Müllerian Hormone (AMH). Any alteration of this equilibrium may induce early follicle depletion and subsequent infertility. Cyclophosphamide (Cy) one of the alkylating agents commonly used for treating breast cancer is able to trigger PMF activation further leading to premature ovarian insufficiency. Preventing chemotherapy-induced ovarian dysfunction might represent an option for preserving optimal chances of natural or medically assisted conceptions after healing.
We showed in a model of Cy-treated pubertal mice, that AMH administration was able to restrain PMF depletion by counting the total PMF number within mouse ovaries. Moreover, the PI3K signaling pathway was evaluated following Cy administration with and without AMH injection. We showed that AMH decreased the phosphorylation of FOXO3A, a transcription factor of PMF activation and induced its nuclear translocation. Altogether, the results support a protective role of AMH against Cy-induced follicular loss. To better understand AMH action in the ovary, we investigated the molecular mechanism to explain the protective effect of this hormone on the PMF pool. It has been reported that autophagy, a lysosomal degradative ubiquitous process implicated in cellular homeostasis, was involved in both ovarian follicular death and survival mostly by PI3K pathway (Gawriluk et al. Reproduction 2011 141, 759–765). We show in mice that Cy inhibits autophagy in the ovary while AMH induces autophagy. In vivo analysis of autophagic flux is currently in progress to dissect this process more finely. Interestingly, FOXO3A was shown to be related to autophagy activation. To investigate the role of FOXO3A in AMH-induced autophagy further, we analyzed mRNA and protein expression of autophagy-related genes controlled by FOXO3A, including BECLIN-1, ATG12, ULK1, BNIP3, GABARAP, and LC3B. These findings establish a close relationship between AMH and autophagy to protect PMF stockpile and to limit follicular depletion induced by Cy.
SAT-293 Osteocalcin and Exercise Improve Mood and Cognition in Female Mice with High-Fat Diet Induced Type 2 Diabetes
Authors: Rentz Jesse , Winberg Jordan , Swardfager Walter , Mitchell Jane 
Published: May 2020

Abstract
The skeleton has been characterized as an endocrine organ, demonstrating a capacity to modulate cognition, mood and energy homeostasis (1,2). These endocrine actions of the skeleton have been attributed to the osteoblast-derived peptide osteocalcin. In mice, uncarboxylated osteocalcin (ucOCN) decreased the acquisition of type 2 diabetes mellitus (T2DM) and ameliorated depressive- and anxiety-like behaviours (1,2). Clinically, T2DM patients present with reduced serum osteocalcin levels and approximately 1 in 4 also suffer from co-morbid depression (3,4). The cognitive and metabolic benefits of ucOCN are similar to the beneficial effects of exercise that is recommended in treatment of both depression and T2DM. Here we compared the effects of ucOCN or exercise in female C57-BL/6J mice under two different metabolic conditions. Mice were fed either a high-fat diet (60% calories from fat) to induce T2DM or a control diet (10% calories from fat). Groups of mice were either sedentary or exercised daily by 30 min treadmill running for two months, with or without daily administration of ucOCN (30 ng/g/day). Mice with T2DM displayed depressive behaviours marked by a higher immobile time in tail suspension tests compared to control mice (97±25 n=11 vs 207±9.0 s n=12; t21=4.21, P=0.0004). Exercise and osteocalcin both improved depressive behaviour (137±8 n=12; t22=5.85, P&lt;0.0001 & 127±15 s n=12; t22=4.46, P=0.0002). Anxiety, measured by the elevated-plus maze revealed the mice with T2DM displayed increased anxiety spending less time in the open arms and had a lower ratio of open to closed arm entries than the control group (0.37±0.03 n=10 vs 0.21±0.032 n=11; t19=3.56, P=0.0021). Neither exercise nor osteocalcin improved anxiety in the T2DM mice. The puzzle box test revealed the negative effects of the high-fat diet in problem solving and memory, where the sedentary mice displayed greater latencies to solve each task compared to control mice. Exercised and mice receiving osteocalcin displayed performances comparable to that of the control group. Under normal metabolic conditions (low fat diet), neither osteocalcin nor exercise altered responses in any of the behavioural tests. Together, these results: 1. The effects of osteocalcin on behaviour and cognition are comparable to that of the effects of exercise in female mice with T2DM; 2. Behaviour and cognition did not improve from exercise or osteocalcin in female mice on a low-fat diet.
References: (1) Ferron et al., Bone. 2012 Feb;50(2):568–575. (2) Oury et al., Cell. 2013 Sep 26:155(1):228–241. (3) Liu et al., Horm Metab Res. 2015 Oct;47(11):813–9. (4) Khaledi et al., Acta Diabetol. 2019 June;56(6):631–650.
SAT-344 Venous Thromboembolism Caused by Primary Hyperparathyroidism
Authors: Kanta Romana , Ansari Mohammad Jamal Uddin , Ali Mariam , Rehman Anis , Jabri Hadoun , Parveen Sanober , Jakoby Michael G 
Published: May 2020

Abstract
Background. Primary hyperparathyroidism (PHPT) is often overlooked as a potential etiology of hypercoagulability and thrombosis. We present a case in which PHPT was the only identifiable risk factor for an episode of venous thromboembolism (VTE).
Case. A 64 year old female with no chronic health problems presented to the emergency department for evaluation of dyspnea and right lower extremity pain. Symptoms had steadily increased in severity over approximately one week. The patient denied any long distance travel, sustained immobility, or tobacco use, and she was not taking any prescription or over-the-counter medications. Examination was notable for right distal lower extremity pain to palpation, but no swelling or erythema was observed. Elevated D-dimer (4.00 mg/mL, &lt; 0.50) and hypercalcemia (12.7 mg/dL, 8.8–10.5) were discovered on initial laboratory testing, and an ECG showed sinus tachycardia. CT angiography of the chest revealed extensive, bilateral pulmonary emboli, and lower extremity venous Doppler studies confirmed a right lower extremity deep venous thrombus (DVT). Unequivocally elevated intact parathyroid hormone (PTH) level (235 pg/mL, 12–88) confirmed a diagnosis of PHPT, and an apparent left lower parathyroid adenoma was identified by both Tc99m parathyroid scintigraphy and neck ultrasonography. After hydration, serum calcium remained in the range of 11.5–12.0 mg/dL. The patient was discharged home on the direct factor Xa inhibitor rivaroxaban (Xarelto™) with a plan for six months of anticoagulation before parathyroidectomy.
Conclusions. The skeletal, neuromuscular, cardiovascular, and neuropsychiatric manifestations of PHPT are well described, but little is published regarding PHPT and VTE. In a multivariate analysis of participants in the fourth and fifth Tromsø surveys controlled for age, sex, and BMI, simultaneous elevations of PTH and serum calcium were associated with a nearly 80% increased risk of VTE. PHPT has been linked to several changes that predispose to a hypercoagulable state and thrombosis including dehydration, vasoconstriction, increased platelet count and levels of coagulation factors VII and X, elevated tissue plasminogen activator inhibitor-1 and D-dimer levels, and diminished tissue factor pathway inhibitor levels. Unfortunately, risk of VTE is not addressed in series documenting long-term outcomes for patients undergoing parathyroidectomy for management of PHPT. However, in cases of VTE where PHPT is diagnosed, parathyroidectomy should be considered to potentially improve hypercoagulability and reduce the risk of subsequent VTE.
SUN-646 A Novel Population of FOXO1-Expressing Cells in the Stomach Controls Cell Plasticity by Regulating the Cyclin CCNE1
Authors: McKimpson Wendy M , Kuo Taiyi , Kitamoto Takumi , Higuchi Sei , Haeusler Rebecca , Accili Domenico 
Published: May 2020

Abstract
A promising new therapy for type 1 diabetes is the reprogramming of gut enteroendocrine cells into cells that produce insulin. The mechanism by which gut epithelial cells are converted into cells that make insulin remains unknown. We have previously found that elimination of Foxo1 in neurogenin3 (Ngn3)-expressing cells of the intestine generates glucose-sensing, insulin-producing cells that are capable of reversing streptozotocin-induced diabetes. Others have reported that stomach cells have a similar property when made to express β-cell factors Ngn3, Pdx1, and MafA. Using mice bearing a Foxo1-GFP knock-in allele, we traced Foxo1-expressing cells in the gut to subpopulations of Ngn3+, as well as acid-secreting parietal stomach cells. To study these cells, we established a 2D co-culture method in which primary stomach cells are isolated from mice and cultured with embryonic fibroblasts. Deletion of Foxo1 in this system generated cells immunoreactive for insulin and C-peptide. Interestingly, Foxo1 ablation also altered the abundance of other gastric cell populations, including more parietal cells and decreased expression of stem cell marker, Lgr5. Tissue-specific elimination of Foxo1 in vivo in either Ngn3+ or parietal cells also resulted in the appearance of insulin+ cells, increased parietal cells, and reduced Lgr5 mRNA. To determine how Foxo1 regulated these changes, we used cells isolated from reporter mice that change from red to green after genetic recombination to collect Foxo1-deleted primary stomach cells using FACS. While the mRNA levels of many known Foxo1 targets did not change, cyclin E1 (CCNE1), which regulates G1 to S-phase progression of the cell cycle, was significantly decreased. Conversely, primary stomach cells overexpressing Foxo1 had increased levels of CCNE1. Finally, using ChIP-seq, we found that Foxo1 binds directly to the CCNE promoter in a nutrient-dependent manner. In summary, we show that Foxo1 is expressed in a subpopulation of stomach parietal cells and that it regulates their function through the cell cycle regulator, CCNE1.
SUN-130 Preoperative Hematological Parameters Associated with Recurrence or Regrowth of Meningiomas
Authors: Leães Rech Carolina Garcia Soares , Minuzzi Ricardo Kunde , Silva Camila Batista de Oliveira , Araújo Bruna , Mafalda Tainá , Ferreira Nelson Pires , Oliveira Miriam da Costa , Pereira-Lima Júlia F Semmelmann 
Published: May 2020

Abstract
Meningiomas represent the most frequently diagnosed intracranial tumors. Inflammation and immune processes may play an important role in therapeutic response as well as in anti- and pro-tumor modulating function. In tumors, inflammatory markers have been able to provide useful prognostic information for treatment or clinical evaluation of patients. The aim of this study was to investigate preoperative hematological markers concerning recurrence or regrowth and clinical variables in meningioma. Eighty nine patients with no corticosteroid therapy were included. Blood tests and tumor characteristics were collected from medical records. Recurrence-free survival was evaluated using Cox regression and Kaplan-Meier curves. Of the 89 cases, 73 (82%) were grade I and 16 (18%) grade II. The mean age was 53±13.9 years, with higher frequency in women, 2:1 proportion. The most frequent subtypes were meningothelial (40.4%), transitional (23.5%) and atypical (17.9%), 64% with peripheral location and 64% had a size greater than 3 cm. Regarding tumor resection, 49 (55.1%) underwent complete surgery (40 remained with tumor (81.6%) and 9 relapse (18.3%)) and 40 (44.9%) submitted to partial resection surgery (29 remained with persistent lesion (72.5%) and 11 regrowth (25%)). In total, 20 (22.4%) cases of recurrence or regrowth were observed. The median recurrence-regrowth free survival (RFS) was 62 months, 96.1% at 1 year, 67.4% at 3 years and 51.2% at 5 years. In univariate analysis, anemia (p=0.04), neutrophilia (p=0.02) and neutrophilis/lymphocyts ratio (NLR) (p=0.03) were associated with an increased risk of recurrence or regrowth and poor RFS. In multivariate, the interaction between anemia and NLR &gt;4 represented a higher risk of recurrence or regrowth (p=0.003). The preoperative presence of anemia, neutrophilia, and NLR was associated with an increased risk of recurrence or regrowth in meningiomas, emphasizing the importance of preoperative evaluation of these parameters.