bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-927 Ectopic Cushing Syndrome Due to a Metastatic Neuroendocrine Tumor to the Breast
Authors: Zhang Jian , Katznelson Laurence 
Published: May 2020

Abstract
Introduction:
We present a rare case of ectopic Cushing syndrome (CS) due to a neuroendocrine tumor (NET) metastatic to the breast.
Case:
A 38-year-old female was referred for ACTH-dependent CS. She had rapid development of cushingoid features and hypertension three months prior to presentation. A 24-hour urinary free cortisol (UFC) was elevated to 2548 μg (0-50 μg/24hr), and ACTH was 228 pg/mL (10-60 pg/mL). A pituitary MRI was normal, and inferior petrosal sinus sampling was not consistent with a central ACTH source. A DOTA-TATE scan showed mediastinal lymphadenopathy and a 0.8cm area of uptake in the right breast. The patient was placed on ketoconazole and UFC normalized. Following biopsy, she underwent breast lumpectomy at an outside hospital, and pathology showed triple negative invasive carcinoma of the breast. Chemotherapy was initiated.
However, her CS rapidly worsened: repeat UFC was 4867 μg, and ACTH was 369 pg/mL. Re-review of her pathology slides at our facility showed that the tumor stained negative for breast markers and positive for markers of NET and ACTH. Ki67 staining was approximately 30%. Chemotherapy for breast cancer was immediately stopped. A follow-up PET-CT continued to show uptake in the mediastinal lymph nodes. FNA of these lymph nodes revealed metastatic NET. In order to maximize control of her CS prior to chemotherapy, she underwent bilateral adrenalectomy (BLA). Afterwards, the patient received 10 cycles of chemotherapy with modified FOLFOX-7 for her NET. Thus far, the tumor burden appears stable, and she has been recommended to hold off on radiation therapy. She is currently taking replacement doses of hydrocortisone and fludrocortisone.
Conclusion:
In this challenging case, determination of source of ACTH hypersecretion led to an initial diagnosis of breast cancer. Primary breast carcinoma with neuroendocrine differentiation has been reported to show significant overlap in pathology with NET metastatic to the breast1. However, worsening of the CS in this case led to consideration of an alternative diagnosis, resulting in diagnosis of an ACTH producing NET metastatic to the breast. Prior to chemotherapy, she underwent BLA, which may lower morbidity and mortality associated with ACTH-dependent CS2, particularly given plan for further chemotherapy.
Reference:
1. Mohanty SK, Kim SA, DeLair DF, et al. Comparison of metastatic neuroendocrine neoplasms to the breast and primary invasive mammary carcinomas with neuroendocrine differentiation. Mod Pathol. 2016;29(8):788-798. doi:10.1038/modpathol.2016.69.2.
2. Morris LF, Harris RS, Milton DR, et al. Impact and timing of bilateral adrenalectomy for refractory adrenocorticotropic hormone-dependent Cushing’s syndrome. Surgery. 2013;154(6):1174-1183; discussion 1183-1184.
SUN-119 Identification of Novel Mirnas Found to Be Differentially Expressed Between ATA Risk Stratification Groups in Papillary Thyroid Carcinoma
Authors: A Luisa Fernanda Olaya , Malek Joanne , Hookins Brodie , Joshi Tripti , Zara Watson , Gargya Ash , Gupta Ruta , Elliott Michael , Chua Elizabeth Lian , McLennan Susan 
Published: May 2020

Abstract
The study of miRNAs in PTC has shown that these molecules can help in the diagnosis, prognosis and also as therapeutic candidates [1]. miRNAs are known to be differentially expressed in PTC compared to non-cancerous tissue and a few studies have shown association with some clinico-pathological features. However, little is known regarding their expression in relation to risk of disease progression. In this study, we examined the expression of miRNAs in patients diagnosed with PTC in association with risk of disease recurrence and/or persistence.
Patients were classified by three endocrinologists to either high (H) or low (L) risk according to ATA Risk Stratification. PTC tissue was micro-dissected from Formalin Fixed Paraffin Embedded (FFPE) tissue for analysis. OPenArray analysis showed that 21 miRNAs were differentially expressed in H-L groups (n=4/grp). qRT-PCR was used to confirm these differences in a larger cohort of PTC (H=46; L=58). This comparison also included comparisons between cancer and normal tissue and investigation of miRNAs known to be differentially expressed (i.e miRNAs 222, 221 and 146b). All analysis was performed in Rstudio using ΔΔCt relative to expression of miR-16 which was not altered by PTC.
By qRT-PCR, only 3 of the 21 miRNAs identified by OpenArray analysis, were differentially expressed in H vs L risk (each P&lt;0.05). These miRNAs are known to be involved in cancer progression pathways but have not been reported in PTC. Individual Receiver Operating Characteristic (ROC) curve analysis of these 3 miRNAs had AUC as follows (miR 1: 0.62, miR 2: 0.62, miR 3: 0.64,) and when analyzed together, the AUC model was improved (AUC=0.76). Examination of cancer vs normal tissue confirmed higher expression miR-146b, miR-221 and miR-222 (each P&lt;0.05). However, these miRNAs were not differentially expressed when H vs L risk were analysed.
In this study, we identified 3 miRNAs with potential utility for the stratification of patients into those with H or L risk disease recurrence/persistence. As the current ATA 3-tiered system used is still a reflection of the continuum of risk that patients have, whether these 3 miRNAs may have the utility to further stratify those in the intermediate group remains to be investigated.
Reference: 1.
Ramírez-Moya, J. and P. Santisteban, miRNA-Directed Regulation of the Main Signaling Pathways in Thyroid Cancer. Frontiers in Endocrinology, 2019. 10: p. 430.
MON-512 The Anti-Cancer Agent, Homoharringtonine, Induces the Sodium Iodide Symporter (NIS) Gene Expression in Culture Cells from Papillary Thyroid Cancer, as Well as Non-Thyroid Cancers
Authors: Kato Kanako 
Published: May 2020

Abstract
BACKGROUND: The therapeutic effect of thyroid cancer by radioiodide treatment is dependent on enhancement of NIS expression by TSH, especially its much greater magnitude in target tissue(s) compared to other healthy tissues. We preliminarily found that a protein synthesis inhibitor cycloheximide (CHX) markedly enhanced NIS mRNA expression, followed by increased iodide uptake, in several cancer cell lines, though CHX is highly toxic for clinical use.
Aims: To evaluate the possibility of clinical application of such a pathway to enhance NIS expression, we tried another weak protein synthesis inhibitor, homoharringtonine (HHT), a natural plant alkaloid already utilized as an anti-leukemia agent, in several human cancer cell lines, including thyroid cancer.
Methods: BHP 2-7 papillary thyroid cancer cells, MCF7 breast cancer cells, and MKN gastric cancer cells were treated with HHT and/or a p38 inhibitor, and harvested for quantitative RT-PCR of NIS.
Results: HHT significantly induced the NIS mRNA expression in all of the cell lines tested, up to 298-fold in BHP cells, 38-fold in MCF7 cells, and 235-fold in MKN cells. Time course experiments indicated a biphasic induction of NIS in BHP cells with two peaks at 48 hours and 96 hours, with the EC50 of 664 ng/mL and 767 ng/mL, respectively. In contrast, NIS induction by HHT was monophasic in MCF7 cells at 24 hours with EC50 of 24.6 ng/mL, as well as MKN cells at 96 hours with EC50 of 255.7 ng/mL. Roles of p38 MAPK in the NIS induction has been reported previously, however, p38 inhibitors, SB239063 (10μM), as well as ML3403 (30μM), did not significantly reduce the NIS expression in HHT-treated BHP cells.
Conclusion: These results indicated that HHT has a potential to enhance NIS expression in some NIS-expressing cancer tissues, including papillary thyroid cancer, although its functionality and efficacy are to be validated. The heterogeneity of response in the NIS expression to HHT in three cell lines could be due to differential mechanisms of NIS gene regulation in different tissues.
MON-098 Risk of Long-Term Endocrine Sequelae in Survivors of Progressing Childhood Optic Pathway Glioma Treated by Upfront Chemotherapy: Preliminary Analyses of 102 Subjects from the French Multicentric BB-SFOP Registry
Authors: Hippolyte Helene , De Carli Emilie , Pellier Isabelle , Rialland Xavier , Coutant Regis 
Published: May 2020

Abstract
For the brain tumor committee of SFCE (Societe ́ Française des Cancers de l’Enfant). Objective: Therapeutic approach favors chemotherapy as the first-line-treatment in progressing OPG. There are few data on long term endocrine outcomes of aggressive OPG treated by upfront chemotherapy. Our main objective was to describe the long-term endocrine sequelae in these patients and to identify potential early predictors of the endocrine involvement. Subjects and methods: Children diagnosed with OPG at an age younger than 16 years from the French multicentric BBSFOP registry were included. They were treated with upfront chemotherapy according to the BB-SFOP protocol in France between June 1990 and December 2004, and subsequent treatment (second-line chemotherapy, surgery, radiotherapy) was used depending on tumor progression. They underwent a late evaluation with clinical and biological assessment between January 2011 and March 2016. Results: One hundred and two patients were included in our study. The mean age at tumor diagnosis was 3.3±0.3 years. The mean time of follow-up was 13.9±3.7 years. A history of precocious puberty was present in 36% of the subjects. At least one endocrine deficiency was present in 93% of the subjects (GHD 74%, TSH deficiency 57%, ACTH deficiency 36%, hypogonadotropism 33%, gonadic deficiency 30%, diabetes insipidus 15%; inappropriate AVP secretion 7%). 37% of males and 39% of females were overweight or obese. Mean adult height, reached in 51 subjects, was -1.2±1.3 SDS in males, and -0.7±1.4 SDS in females. Chemotherapy only was protective from pituitary deficiencies (odds ratio 0.19 to 0.37, P &lt; 0.05). NF1 was protective from TSH and ACTH deficiencies (odds ratio 0.25 to 0.35, P &lt; 0.05). Tumor volume on diagnostic MRI was not predictive of pituitary deficiencies. Gonadic deficiency was significantly more frequent in males than females (46,5% vs 12.2%, P &lt; 0.05), and associated with chemotherapy only (OR 3.2, P &lt; 0.05) and NF1 (OR 4.8, P &lt; 0.05). Overweight/Obesity was associated with ACTH deficiency (OR 5, P &lt; 0.05).Conclusion: Obesity and late endocrine dysfunction were frequent in subjects treated by upfront chemotherapy for aggressive OPG during childhood. However, chemotherapy only, when possible, was protective from pituitary involvement.
SAT-399 Baseline Characteristics from the Observational PARADIGHM Registry of Patients with Chronic Hypoparathyroidism
Authors: Clarke Bart L , Rejnmark Lars , Ing Steven W , Brandi Maria Luisa , Björnsdottir Sigridur , Hofbauer Lorenz C , Houillier Pascal , Khan Aliya A , Levine Michael A , Mannstadt Michael , Shoback Dolores M , Vokes Tamara J , Zhang Pinggao , Marelli Claudio , Germak John , Gittoes Neil 
Published: May 2020

Abstract
PARADIGHM is an actively recruiting, prospective, observational registry (NCT01922440/EUPAS16927). The primary objective is to evaluate the safety and effectiveness of recombinant human parathyroid hormone, rhPTH(1-84), treatment in patients with chronic hypoparathyroidism (HypoPT) under routine clinical care. The secondary objective is to characterize the clinical course of chronic HypoPT under conditions of routine clinical practice. At enrollment, registry inclusion criteria are patients having a HypoPT diagnosis &gt;6 months and receiving conventional therapy (CT; eg, calcium supplements and active vitamin D), rhPTH(1-84) plus CT, or rhPTH(1-84). We present baseline characteristics of patients as of a June 30 2019 data cut. Baseline was defined as the value entered at the time of enrollment (Visit 1). Baseline symptom data exclude patients who initiated rhPTH(1-84) prior to enrollment (n=68) and are herein presented as two groups: those subsequently prescribed with rhPTH(1-84) after enrollment or those treated with CT. All data are summarized descriptively. Patient data from 64 centers in Europe and North America were analyzed. In the analysis population (n=737), 587 patients (79.6%) were female, 620 (84.1%) were white, and the mean (SD) age was 49.1 (16.45) years. The mean (SD) BMI was 19.3 (5.73) kg/m2 and 30.0 (7.72) kg/m2 in patients aged &lt;18 (n=25) and ≥18 (n=587) years, respectively. The primary cause of HypoPT was thyroid surgery (n=547 [74.2%]; of these, 281 [60.0%] underwent surgery for thyroid cancer). Endocrinologists were the prescribing specialists for most patients (n=660 [89.6%]). Vitamin D and analogs were prescribed for 90.1% of patients (calcitriol, 74.2%, native vitamin D, 47.4%, alfacalcidol, 7.9%,), calcium for 81.0% (calcium carbonate, 57.9%, calcium citrate, 27.1%), and thyroid hormones for 71.2% (levothyroxine, 73.4%; liothyronine, 5.8%). Symptoms reported at enrollment for the rhPTH(1-84) (n=66) and the CT groups (n=603), respectively, included fatigue (53.0%, 39.3%), paresthesia (48.5%, 29.2%), muscle twitching (48.5%, 21.1%), muscle cramping (40.9%, 33.0%), headaches (33.3%, 17.6%), anxiety (28.8%, 20.1%), muscle pain (28.8%, 19.2%), tetany (28.8%, 12.1%), and brain fog (27.3%, 16.3%). The baseline data for the overall population appear to be representative of patients with chronic HypoPT. Baseline data suggest that at enrollment patients prescribed rhPTH(1-84) after enrollment appear to have an increased burden of disease than patients receiving CT based on symptoms. PARADIGHM will be a valuable resource of real-world longitudinal data for patients with chronic HypoPT.
MON-167 Use of a Morning Cortisol Level to Predict Recovery of the Hypothalamic-Pituitary-Adrenal (HPA) Axis in Secondary Adrenal Insufficiency Following Remission of Cushing’s Syndrome
Authors: McGlotten Raven , Nieman Lynnette K 
Published: May 2020

Abstract
BACKGROUND: Remission of Cushing’s syndrome (CS) is generally defined as morning serum cortisol values &lt;5mcg/dL (&lt;138 nmol/L) or Urine Free Cortisol &lt;10-20ug/dL (&lt; 28 – 56 nmol/d) after tumor resection, which reflects suppression of the hypothalamic-pituitary-adrenal (HPA) axis by sustained hypercortisolism. Endocrine Society guidelines recommend glucocorticoid replacement until the HPA axis is normal as assessed by a morning (AM) or post-ACTH stimulation test cortisol level of approximately 18 ug/dL (500 nmol/L) or greater (1). Patients with subnormal cortisol levels remain on glucocorticoid until retested in 3-6 months. The goal of this study was to determine whether a baseline cortisol value predicts a normal response to the ACTH stimulation test.
Methods: We reviewed 235 ACTH stimulation (stim) tests conducted on 76 patients with secondary adrenal insufficiency following remission of CS. Patients had resection of a single adrenal gland (n=7), pituitary adenoma [with (n=3) or without (n = 47) subsequent radiation], 70% of pituitary tissue (n=5), or ACTH secreting intrathoracic tumor (n=13). One had an ectopic ACTH secreting tumor in spontaneous remission (n=1). ACTH stim tests were conducted between 0800h and 0900h, 24 hours after the last dose of glucocorticoid, using 250 mcg of cosyntropin intravenously. Cortisol levels were measured just before administration of cosyntropin, and 30 and 60 minutes afterwards. Patients were considered to have passed the test if baseline or peak cortisol values reached &gt; 18mcg/dL. Baseline cortisol values were compared to the ‘pass’ rate.
Results: Baseline F values (ug/dL) and passing rates (# pass/total) were:
&lt;4: 1/91;
4-4.9: 2/27;
5-5.9: 8/31;
6-6.9: 2/21;
7-7.9: 7/25;
8-8.9: 4/12;
9-9.9: 8/12;
&gt;10 - &lt; 15: 6/11
15 – 19.5: 5/5
Thus, Am cortisol values &gt;9 ug/dl were significantly more likely to predict a normal response to ACTH stim than lower values (p&lt;0.0001). ACTH values (n=184) did not predict peak F levels. However, no patient with ACTH value &lt;5 pg/ml passed the test; all had peak F values of 0-10.5.
Conclusion: Baseline cortisol can be a guide as to whether the more costly stimulation test is needed. In the small cohort with baseline 0800h – 0900h cortisol &gt;15 ug/dL, all passed the test, suggesting that it is not needed in such patients. We recommend use of an ACTH stimulation test to assess recovery of the HPA axis when a morning cortisol reaches 9 mcg/dL, with an expected pass rate of about 66%.
Reference: 1. Nieman LK, Biller BM, Findling JW, Murad MH, Newell-Price J, Savage MO et al. Treatment of Cushing’s Syndrome: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 100:2807, 2015.
SAT-734 HSD3B1 Expression in the Human Immune System
Authors: McManus Jeffrey M , Le Thi Hong Nga , Min Booki , Asosingh Kewal , Zein Joe , Erzurum Serpil , Sharifi Nima 
Published: May 2020

Abstract
3β-hydroxysteroid dehydrogenase-1 (3βHSD1), catalyzing conversion of dehydroepiandrosterone (DHEA) to Δ 4-androstenedione, is an essential enzyme in the pathway toward production of biologically active androgens such as dihydrotestosterone from the adrenally produced precursor DHEA sulfate, the most predominant steroid hormone in circulation. We previously identified, in the gene (HSD3B1) that encodes 3βHSD1, a germline gain-of-function missense-encoding variant that has now been validated in several studies as predicting more rapid progression in prostate cancer patients treated with gonadal testosterone deprivation. Production of androgens from adrenal precursors is important not just in the context of prostate cancer but in other physiologic and pathophysiologic processes, which could include asthma. Androgens are associated with better lung function in both asthma and healthy cohorts, and increasing circulating androgen levels in males help explain the switchover in asthma being more common in boys than girls but then more common in women than men. A main treatment for asthma, as well as other inflammatory processes, is administration of glucocorticoids, yet unresponsiveness to glucocorticoids in a subset of patients remains a major problem. Systemic glucocorticoid administration suppresses adrenally produced DHEA and DHEA-S, suggesting a depleted pool for biologically active androgen production as a mechanism for glucocorticoid resistance. Our surprising preliminary data support a link between glucocorticoid responsiveness and the more active HSD3B1 allele: patients homozygous for the adrenal-permissive HSD3B1(1245C) allele exhibit better response to oral glucocorticoids than those homozygous for the adrenal-restrictive HSD3B1(1245A), with heterozygous patients falling in the middle. This suggests a model in which patients with the more active (adrenal-permissive) form of 3βHSD1 produce sufficient androgens despite the depleted pool of precursor hormones whereas patients with the less active (adrenal-restrictive) form cannot. To further elucidate the link between 3βHSD1 activity and immune response, we assayed HSD3B1 expression in different types of white blood cells. Leukocyte subsets from asthma patients and healthy controls were purified using fluorescence-activated cell sorting, and HSD3B1 expression was analyzed using qPCR. White blood cells of several types expressed HSD3B1 at levels comparable to or greater than both prostate cancer and placental choriocarcinoma cell lines with very robust 3βHSD1 activity. Further determining the cell type specific expression and activity of this key enzyme is an important step in unraveling the link between the HSD3B1 polymorphism and asthma along with potentially many other immune processes.
SUN-160 Development of Adrenocortical Carcinoma in an Adrenal Nodule After Nine Years of Size Stability on Imaging: A Case for Critical Review of Efficacy of Radiographic Size Criteria
Authors: Tam Matthew , Sharma Sona 
Published: May 2020

Abstract
BACKGROUND: Current consensus guidelines for adrenal incidentalomas smaller than 4 cm recommend re-evaluation up to 2 years. Although there is no consensus for imaging surveillance beyond 2 years, in general, stability in size over time is considered a sign of benign nature.
Clinical Case: A 50-year-old African-American woman presented to Endocrinology for resistant hypertension since age 30 and an enlarging right adrenal nodule. She was obese, weighing 138.8 kg with a BMI of 55.97 kg/m2, without clinical Cushingoid features. At her first visit she was taking the following antihypertensives: amlodipine, losartan, hydrochlorothiazide, and clonidine patch. She took no other prescription medications. Her baseline metabolic blood profile was normal. Further testing revealed a profile consistent with possible primary hyperaldosteronism and subclinical Cushing’s syndrome: plasma aldosterone 17 ng/dl, plasma renin activity 0.232 ng/ml/hour, ACTH 10 pg/ml, AM cortisol 8.3 mcg/dl, DHEAS 30 mcg/dl, and 1mg dexamethasone suppression test resulted in cortisol of 7.6 mcg/dl (normal &lt; 1.8 mcg /dl) with a simultaneous dexamethasone level of 357 ng/dl (140 – 295 ng/dl). However, 24-hour urinary free cortisol and urinary metanephrines were within reference ranges. Further confirmatory tests were not performed due to her imaging findings, as described below.
The earliest abdominal imaging was a CT abdomen with contrast in 2005 which measured a 2.1 cm right adrenal mass. For various reasons she had repeat CT contrast imaging in 2006, 2007, 2012, and 2014 demonstrating no changes in the dimensions of her adrenal nodule, noting all the studies were performed with contrast only and without Hounsfield unit (HU) measurements. In 2017, a CT abdomen with adrenal protocol demonstrated a right adrenal mass measuring 4 cm x 3.5 cm (increased from 2.1 X 1.2 cm in 2014), characterized by 43 HU pre-contrast, 71 HU post-contrast, and an absolute washout of 29%. Due to high suspicion for malignancy, a PET-CT was performed with FDG, which revealed high uptake in the right adrenal mass.
She was referred for a right adrenalectomy and pathology showed adrenocortical carcinoma with some infiltration into adipose tissue. There was a high mitotic index (42 per 50 high powered fields) and Ki67 of 35%, classified as Stage III pT3NxM0. She was referred to oncology and treated with external radiation to the adrenal bed along with initiation of mitotane.
Conclusion: This case infers that long-term size stability of an adrenal nodule does not confer full confidence of a benign process. Compared with previous reports in the literature describing long latencies for ACC, this is one of the longest records of size stability over 9 years followed by a size increase 3 years later.