bluuebunny/crossref_metadata_2025 huggingface dataset:
SUN-222 Pre- and Post-Pubertal Reference Ranges for Oxygenated Androgens in Saliva
Authors: Adaway Joanne , Eisenhofer Graeme , Huebner Angela , Krone Nils , McTaggart Malcolm , Peitzsch Mirko , Keevil Brian George
Published: May 2020

Oxygenated androgens such as 11 β-hydroxyandrostenedione (11OHA4) and 11-ketotestosterone (11KT) contribute significantly to the androgen pool in humans and their measurement has been shown to be useful in diagnosing disorders such as polycystic ovarian syndrome or premature adrenarche and also in monitoring treatment of congenital adrenal hyperplasia, alongside the classical androgens. Their measurement in saliva is particularly advantageous due to the non-invasive nature of sampling, meaning samples can easily be taken regularly to monitor treatment; however reference range data is not currently available for 11OHA4 and 11KT, limiting their clinical use. These analytes were measured in saliva samples from pre and post-pubertal males and females to inform reference ranges for these analytes. Samples collected into salivettes as part of the PRIMMS study (Technische Universität Dresden) were used for this work. A total of 130 samples (35 from pre-pubertal females, 43 from post-pubertal females, 42 from pre-pubertal males and 20 from post-pubertal males) were analysed for 11OHA4 and 11KT by LC-MS/MS. The ages of the participants ranged from 3.77 to 14.0 years in the pre-pubertal samples and 13.9-17.9 years in the post-pubertal samples. Pubertal status was determined clinically. The upper cut-off of the reference interval for 11OHA4 was 560 pmol/L in pre-pubertal females and 590 pmol/L in males, whilst 11KT had an upper limit of 216 pmol/L in females and 205 pmol/L in males. The upper limits of the ranges were higher in post-pubertal samples, with ranges of up to 1542 pmol/L in females and 1775 pmol/L in males for 11OHA4; the ranges for 11KT were up to 654 pmol/L for post pubertal females and 585 pmol/L for post-pubertal males. The data shows, as expected, a rise in the 11 oxygenated androgens post puberty. The upper limits of reference intervals for both analytes were very similar in males and females both pre- and post pubertally. These data can be used to inform clinical interpretation of the 11-oxygenated androgens; further work is required with larger cohorts of samples to develop more robust reference ranges.
SUN-208 The Intra-Individual Variability of 11-Ketotestosterone and 11β-Hydroxyandrostenedione
Authors: Hawley James , Keevil Brian George
Published: May 2020

Background

Emerging evidence has suggested the 11-oxygenated steroids may be important in the diagnosis and monitoring of hyperandrogenism. Two in particular, 11-ketotestosterone (11KT) and 11β-hydroxyandrostenedione (11OHA4) have been implicated in polycystic ovary syndrome, congenital adrenal hyperplasia, precocious puberty and castration resistant prostate cancer. Despite the interest in these analytes, some of their more fundamental properties have yet to be determined. At present, no data is available that quantifies the biological variation of 11KT and 11OHA4 within individuals over time, this may be important as we look to establish normative reference ranges for these potentially useful analytes.

Objective

Here we sought to define the intra-individual variability of 11KT and 11OHA4 in serum using LC-MS/MS.

Method

Blood was collected from 18 healthy volunteers (8 males, 10 females) on the same day each week over a 10 week period using standard venepuncture technique. After collection, the samples were centrifuged within 1 hour, aliquoted and stored at -20°C (-4°F) prior to analysis. All samples from individual volunteers were analysed by LC-MS/MS in triplicate within the same batch so as to limit analytical variability.

Results

The mean analytical coefficient of variation (CV%) for the triplicate analysis was 3.2% for 11KT and 3.7% for 11OHA4. No significant difference was observed between the variability of 11KT concentrations in the male and female cohorts; total intra-individual variation for 11KT was 18.0%. Concentrations of 11OHA4 were more variable in the male cohort when compared to the female cohort. This was reflected by differences in their respective intra-individual variations of 32.5% vs 24.8%.

Summary

Intra-individual variation is an important consideration when interpreting patient results. Concentrations of 11KT were tightly regulated in both the male and female cohorts with no clear demarcation between the two groups. Although concentrations of 11OHA4 were prone to greater variation over the 10 week period, considerable overlap was observed between the male and female subjects. Our data suggests that 11KT and 11OHA4 concentrations are not significantly affected by the menstrual cycle.
SUN-052 Effects of Cross-Sex Hormone Therapy on Lipid Metabolism in Transgender Women and Men
Authors: Kelley Carly , Coviello Andrea D
Published: May 2020

Sex hormone therapy in cisgender persons (i.e. postmenopausal women and hypogonadal men and women) leads to changes in lipid metabolism and weight, but it is unclear to what extent this occurs in transgender persons receiving higher doses of cross-sex hormone therapy (CSHT) for the purpose of gender transition.Objective: To determine changes in lipid metabolism among transgender women (TW) and transgender men (TM) on CSHT.Methods: We conducted a retrospective chart review of patients identified at a transgender-specific clinic within an academic medical center. Data were collected on age, ethnicity, hormone therapies, lipid lowering therapy (LLT), surgical status, lipid panel, A1C, LFTs, BMI, and weight before and after initiation of HT. Patients on stable LLT were included but those with LLT initiated after baseline observation were excluded. Changes from baseline to post CSHT in TW and TM groups were evaluated with paired t-tests.Results: We identified 18 TW and 22 TM for whom laboratory data were available. Mean±SD age of TW was 33±13 years and for TM was 28±12 years; the majority (78%) were Caucasian. Mean±SD duration of HT in TW was 10.1±4.5 months and in TM 6.7±4.4 months. No patients had undergone gonadectomy at any time prior to or during the data collection period. One TW and one TM were on stable LLT during the observation period. All TW were treated with estradiol (78% oral, 11% patch) and spironolactone. In TW, there was a significant 10% increase in HDL from 48±17 mg/dl to 53±15 mg/dl (p=0.02) but there were no significant changes in other lipid fractions, A1c, or weight/BMI. The majority of TM (82%) were treated with weekly intramuscular testosterone-esters injections and the remainder with daily testosterone gel. More substantial and unfavorable metabolic changes occurred in the TM with a 15% decrease in HDL from 55±15 mg/dl to 47±10 mg/dl (p=0.004), increase in A1c from 5.07±0.45% to 5.22 ± 0.39%(p=0.04), increase in BMI from 29±10 kg/m2 to 31±10 kg/m2 (p=0.002), and a trend toward increased triglycerides (96±64 mg/dl to 110±80 mg/dl, p=0.07). Hemoglobin and hematocrit significantly increased in TM but there was no significant change in LFT in either group. Limitations include lack of data on body composition to determine relative changes in adipose tissue or muscle mass in relation to weight changes and small sample size.Conclusion: Our study suggests that CSHT has a neutral to slightly favorable impact on lipid metabolism in TW and a negative impact on lipids and glucose in TM. Larger, prospective studies are needed to determine whether these changes persist over the longer duration of CSHT and whether this translates to an increased risk of cardiovascular disease and mortality. Clinicians should inform TM patients about these potential negative effects of CSHT on lipid metabolism so that their patients can adopt healthy lifestyle interventions early on to optimize their cardiovascular risk.
SUN-651 Murine Cecal Ligation and Puncture (CLP) Perturbs Phosphorylation of Insulin Receptor Substrate 2 (IRS-2)
Authors: Mathew Deepa , Barillas Julia , Fernandes Tiago , Kelly Alexander , Yaipen Omar , Abraham Mabel , Deutschman Clifford
Published: May 2020

Hyperglycemia is a characteristic finding in sepsis, and its presence worsens outcome (1). Patients with sepsis need larger doses of insulin to reduce glucose levels. This abnormality has been termed “insulin resistance” but the molecular mechanism by which sepsis attenuates the insulin signaling pathway is unknown. Previous work has shown impairment of phosphorylation in several intracellular signaling pathways following CLP, a well-validated murine model of sepsis (2). Phosphorylation of tyrosine in IRS-2 is essential for functional insulin signaling in hepatocytes (3). Therefore the aim of this study was to investigate the effects of CLP on IRS-2 phosphorylation.

Hypothesis: CLP attenuates phosphorylation of IRS-2.

Methods: All studies were approved by the Feinstein IACUC and conformed to ARRIVE guidelines. CLP was performed on C57Bl6 mice. Before CLP, animals were identified for sacrifice at specific post-procedure time points. To stimulate phosphorylation of IRS-2, insulin was injected in control and CLP mice at 24 and 48 hours post CLP. Following sacrifice, protein was isolated from liver tissue. Protein abundance was determined using immunoblotting. The detection of the phosphorylated form of these proteins was determined by enzyme-linked immunosorbent assay (ELISA) with a phospho-insulin receptor antibody. Statistical significance was determined using ANOVA for repeated measures with a Sidak post-hoc correction.

Results: Relative to the control, tyrosine phosphorylation of IRS-2 was significantly (p<0.05) reduced at 24 and 48 hours following CLP.

Conclusions: Tyrosine phosphorylation of hepatic IRS2 is attenuated at early time points following CLP. These results are consistent with other studies examining the effects of CLP on intra-cellular signal transduction pathways (1). Further, these results provide evidence that changes in the insulin signaling transduction underlie CLP-induced “insulin resistance”.

References: (1) Abcejo et al., Crit Care Med. 2009;37(5):1729-1734. (2) van den Berghe et al, NEngl J Med. 2001;345(19):1359-1367. (3) Valverde et al., Diabetes 2003 Sep; 52(9): 2239-2248.
OR09-06 HNRNPA2B1 Mediates Endocrine-Sensitivity and Alters PSAT1 in Breast Cancer Cells
Authors: Klinge Carolyn M , Piell Kellianne M , Clem Bran F , Petri Belinda J
Published: May 2020

Higher expression of the RNA binding protein HNRNPA2B1 (Heterogeneous Nuclear Ribonucleoprotein A2/B1), a reader of the N(6)-methyladenosine (m6A) mark in transcribed RNA, is found in endocrine-resistant, estrogen receptor (ERα)+ LCC9 and LY2 breast cancer cells derived from MCF-7 endocrine-sensitive luminal A cells (1). HNRNPA2B1 interacts with DGCR8 in the DROSHA complex to promote processing of pri-miRNAs to pre-miRNAs. We identified HNRNPA2B1-regulated miRNAs by RNA seq and target pathways, including serine family amino acid metabolic processes, TGFβ signaling, response to estrogen, and cell junction by MetaCore enrichment pathway analysis (1). Stable 4.5-fold overexpression of HNRNPA2B1 in MCF-7 cells (MCF-7-A2B1 cells) results in ablation of growth inhibition by 4-hydroxytamoxifen (4-OHT) and fulvestrant. This was not due to loss or decrease of ERα; in fact, ERα was increased ~ 1.6-fold. Conversely, transient knockdown of HNRNPA2B1 expression in LCC9 and LY2 cells sensitized the cells to growth inhibition by 4-OHT and fulvestrant, without changing ESR1 expression. MCF-7-A2B1 cells showed increased migration, reduced E-cadherin and increased vimentin, suggestive of EMT; however, they exhibited reduced clonogenic survival. Follow-up on the identification of HNRNPA2B1-miRNA regulation of the serine pathway revealed higher expression of phosphoglycerate dehydrogenase (PHGDH) and phosphoserine aminotransferase (PSAT1) transcripts and proteins in LCC9, LY2, and MCF-7-A2B1 compared to MCF-7 cells. We identified two miRNAs, miR-424-5p and miR-145-5p downregulated in MCF-7-A2B1 cells that directly targeted the PSAT1 3’UTR in dual luciferase assays. Lower miR-424-5p and miR-145-5p in endocrine-resistant LCC9 and LY2 correlate with increased PSAT1 and higher PSAT1 is associated with reduced overall and metastasis-free survival in breast cancer patients. Overall, our data suggest a role for increased HNRNPA2B1 in tamoxifen-resistance. Reference: (1) Klinge CM, Piell KM, Tooley CS, Rouchka EC. HNRNPA2/B1 is upregulated in endocrine-resistant LCC9 breast cancer cells and alters the miRNA transcriptome when overexpressed in MCF-7 cells. Sci. Rep. 2019; 9:9430.
SAT-162 Potential Diagnostic Use of a Steroid Profile in Patients with Poorly Controlled Diabetes Mellitus
Authors: Fecteau Kellie , Giori Luca , Esteller-Vico Alex , Eiler Hugo
Published: May 2020

Cushing’s syndrome may contribute to insulin resistance and impaired insulin secretion in patients with diabetes mellitus. The prevalence of Cushing’s syndrome in human patients with type II diabetes mellitus has been reported as high as 9.4% (1), and prevalence of diabetes mellitus as a complication of Cushing’s syndrome has been reported as high as 50% (2). In our laboratory, evaluation of steroid profiles (analysis of cortisol, progesterone, 17-hydroxyprogesterone, androstenedione, estradiol, testosterone, and aldosterone at baseline and post-ACTH) in 3,600 dogs over 2 years revealed 2% to 8% of dogs with diabetes mellitus had concurrent hyperadrenocorticism. These steroid profiles in dogs with uncontrolled diabetes mellitus, despite insulin therapy, implicated elevated estradiol, progesterone, and 17-hydroxyprogesterone concentrations, with or without elevated cortisol, as probable contributors to poor control of glycemia. It has been reported that high doses of estradiol can decrease expression of insulin receptors in target tissues (3) and progesterone can decrease GLUT 4 expression in target tissues and modulate beta cell proliferation in the pancreas (4), thereby contributing to insulin resistance and possibly insulin secretion. In human patients, decreasing cortisol concentration in Cushing’s syndrome improves the glycemic state in many, but not all gain normoglycemia (5). It is suspected, that for some human patients, cortisol is not the only steroid involved in hyperglycemia and a steroid profile may be a useful diagnostic tool for investigating other steroids contributing to insulin resistance. References: (1) Nieman, Endocrinol Metab Clin N Am. 2018; 47:259-273. (2) Giordano et al., Eur J Endocrinol. 2014; 170:311-319. (3) Gonzalez et al., Steroids. 2002; 67:993-1005. (4) Branisteanu et al., TRENDS Endocrinol Metab. 2003; 14:54-56. (5) Rogowicz-Frontczak et al., Endokrynol Pol. 2017; 68:334-342.
SAT-359 Hypercalcemia - Is This Sarcoidosis, Hyperparathyroidism, or Both?
Authors: Veeramachaneni Ravali , Sandhu Harjyot , Gilden Janice L
Published: May 2020

Hypercalcemia (HC) is a common clinical problem. Among all causes of HC, primary hyperparathyroidism (HPT) and malignancy are the most common, accounting for >90 % of cases. We present a case of HC in a patient attributed to long-standing history of Sarcoidosis (SC) and later found to also have HPT with Parathyroid Adenoma (PA) and Vitamin D Deficiency.

A 64-year-old female presented to the emergency room for social needs. She had not received medical care for the past 10 years and had known history of SC, previously treated with prednisone and methotrexate. She also noted a long-standing history of elevated calcium (Ca) up to 11 mg/dL. She was fasting for the past 1 month for spiritual reasons and was not taking any medications or supplements. Initial labs were significant for Ca of 13.2 mg/dL, Albumin 4.4 g/dL, ionized Ca 1.43 mmol/L. Creatinine was 1.1. EKG revealed T-wave inversions in V1, 2, 3. She received IV fluids and Ca improved to 11 mg/dL. HC was attributed to known history of SC. However further evaluation revealed parathyroid hormone (PTH) level high at 156 pg/mL, 25-OH Vit D level low at 8.5 ng/mL with normal 1,25 hydroxy Vit D levels at 46 pg/mL. Parathyroid sestamibi scan revealed a left parathyroid adenoma. Surgery was deferred because patient was asymptomatic and did not meet criteria for parathyroidectomy. On discharge, Ca levels remained stable and she was started on Ergocalciferol 50,000 units weekly.

HC can be either parathyroid mediated, non-parathyroid mediated, or due to medications. In primary HPT, the elevated PTH levels cause increased bone resorption through activated osteoclasts and increased intestinal Ca absorption. Malignancies involving solid tumors and leukemias can lead to HC through osteolysis and osteoclasts or PTH-related peptide. Thiazide diuretics increase renal Ca absorption that lead to mild HC which can be reversed when the medication is discontinued. Other endocrine disorders that can lead to HC include thyrotoxicosis-induced bone resorption, adrenal insufficiency and pheochromocytoma.

Management of hypercalcemia depends upon the level of Ca. Mild HC (Ca < 12mg/dL) is usually asymptomatic and improves with hydration. Asymptomatic or mildly symptomatic patients with chronic moderate HC (Ca 12-14 mg/dL) may not require immediate treatment. Severe HC (Ca >14mg/dL) is treated with IV hydration with normal saline (NS), calcitonin and zolendronic acid. Administration of calcitonin and NS results in substantial reduction in Ca within 12-48 hours.

Although, HC was initially attributed to SC, primary HPT and low 25-OH Vit D levels also contributed to HC in this patient. Thus, it is important to evaluate patients with known HC from sarcoid for other etiologies.
MON-478 Impaired Sensitivity to Thyroid Hormone - A Diagnostic and Therapeutic Challenge
Authors: Pedro Jorge , Gorito Vanessa , Ferreras Cristina , Maria Ferreira João Silva , Ferreira Sofia , Costa Carla , Silva Rita Santos , Correia Cíntia Castro , Fontoura Manuel
Published: May 2020

Background: Impaired sensitivity to thyroid hormone refers to any process that negatively affects its action, including defects in its transport, metabolism and action on the receptor. Resistance to thyroid hormone due to beta-receptor mutations (RTH-beta) is the most common form of this entity and is characterized by reduced response of peripheral tissues to the action of thyroid hormone. The genetic variability of cofactors involved in the action of thyroid hormone explains the heterogeneity of resistance among affected individuals. Generally, patients with this disorder, have increased levels of free T4 and free T3 in association with normal or high TSH. Clinical case: 11-year-old boy, with personal history of Attention-deficit/hyperactivity disorder (ADHD). A pediatric endocrinology consultation was requested to evaluate abnormalities in his thyroid function tests. A few months earlier, his father was referred to endocrinology consultation because of thyroid function tests abnormalities: TSH - 3.01 μIU / mL (N: 0.35 - 4.94); Free T4 1.7 ng / dL (N: 0.7-1.48); Free T3 4.77 pg / mL (N: 1.71-3.71). Initially, two diagnostic hypotheses were considered: central hyperthyroidism or impaired sensitivity to thyroid hormone. The adult underwent pituitary magnetic resonance, which raised the hypothesis of a pituitary microadenoma, and TRH stimulation test, whose result was strongly suggestive of the second diagnostic possibility. A genetic study was requested and the presence of the c700 G> A variant (p. Ala 324 trh) in the THRB gene was identified, which confirmed the most likely hypothesis. At the time of the pediatric endocrinology consultation, the 11-year-old boy had the results of his lab tests: TSH - 6.67 μIU / mL (N: 0.35 - 5); T4L 2.27 ng / dL (N: 0.88-1.58); T3L 7.79 pg / mL (N: 2-4.20). Given his perfect height and weight evolution and the absence of symptoms suggestive of hypo or hyperthyroidism, it was decided not to start any medication, keeping only periodic surveillance. Conclusion: This case exemplifies unusual thyroid function tests. This discordance between serum thyroid hormone and TSH concentrations should raise the possibility of impaired sensitivity to thyroid hormone. In this condition, patients may present with symptoms of hypo or hyperthyroidism and the etiology of thyroid function tests abnormalities are not easily recognized. This can lead to misdiagnosis and consequently unnecessary treatment.
SUN-575 Levels of Nesfatin-1 in Adolescents, and Its Association with Body Mass Index and Risk of Cardiovascular Disease
Authors: Gutierrez Karla Paola , Kornhauser Carlos , Gómez Armando , Luevano-Contreras Claudia , Fafutis-Morris Mary , Gugliucci Alejandro , Garay-Sevilla Ma Eugenia
Published: May 2020

Nesfastin-1 is a recently discovered anorexigenic neuropeptide, which seems to follow the signaling pathway of melanocortin, and is involved in cardiovascular regulation (1). It is expressed in several tissues, including pancreatic islet cells, the central nervous system, In subcutaneous and visceral fat tissue, among others (2). There are few and controversial data that assess the levels of nesfatin-1 and its relationship with the cardiovascular disease. The aim of this study was to evaluate the serum levels of nesfatin-1 in adolescents with different metabolic status and BMI and its association with cardiovascular risk factors (glucose, lipid profile).

Material and methods: This cross-sectional study included adolescents between 15 and 19 years old, classified in 3 groups according to BMI and HOMA-IR: adolescents with normal weight without metabolic alterations (n ​​= 30), metabolically healthy obese (MHO) n = 30 and metabolically unhealthy obese adolescents (MUO) n = 42. Anthropometric measurements were performed, a fasting blood sample was taken to quantify glucose, lipid profile and creatinine. Insulin and nesfatin-1 concentrations were measured by ELISA. Statistical tests employed were Kruskal Wallis, Spearman correlation.

Results: the group of adolescents MUO had higher levels of total-C (p<0.0002); triglycerides (p<0.00001) compared to the control and MHO; higher levels of nesfatin-1 (p=0.0002) and lower levels of HDL-C (p<0.002) compared to the control group. A positive correlation was between nesfatin-1 and BMI (p<0.001), triglycerides (p<0.027), and HOMA-IR (p<0.025) and negative correlation with HDL-C (p<0.026)

Conclusion: Our results show that metabolically unhealthy obese adolescents have higher concentrations of nesfatin-1, showing an association with traditional cardiovascular risk factors, which could lead to the development of cardiovascular disease.

Nothing to disclose GK, KC, GOA, LCC, FMM, GA, GSME

Sources of research support: Grant University of Guanajuato (DAIP 302/2018)

References: (1) Oh-I et al., Nature. 2006; 443:709–712. (2) Stengel A et al., Regulatory Peptides. 2010; 163:18–23
SAT-276 Co-Secreting TSH and Growth Hormone Pituitary Adenoma
Authors: Eid Hatem
Published: May 2020

Introduction: Secreting pituitary adenoma is exceedingly rare. Less than 15 cases having been reported. Its clinical presentation and diagnosis is challenging. We report a case of pituitary macroadenoma, with features of acromegaly and hyperthyroidism. Case report: A 75 years’ old man presented with new onset atrial fibrillation. He had high FT4 with normal TSH. His ultrasound scan of the neck showed a solitary nodule. He had ablation twice and was started on bisoprolol and anticoagulant. He had MRI scan for headaches and this showed a pituitary macroadenoma. He had high IGF-1. His oral glucose tolerance showed failure of GH suppression. His FT4 was persistently high with normal TSH and he had high a subunits. This suggested the diagnosis of TSH and GH secreting pituitary adenoma. Discussion: TSH-secreting pituitary adenomas are rare and not uncommonly, they co-secrete other pituitary hormones including growth hormones. Somatotrophs and lactotrops share common transcription factors with thyrotrophs. TSH-secreting adenomas are benign but 60% of them are locally invasive. TSH-secreting pituitary adenomas typically present with either symptoms of tumor growth like headache or visual field disturbance or symptoms of hyperthyroidism. Thyroid nodules are common in patients with TSHomas. In patients with TSH-secreting pituitary adenomas, majority will need only surgery and radiation. The medical treatment used to normalize TSH and FT4 levels is somatostatin analogs. This is effective in about 90% of patients with TSH secreting pituitary adenomas TSHoma should be differentiated from resistance to thyroid (RTH). The main difference between TSHoma and RTH is the presence of signs and symptoms of hyperthyroidism in patients with TSHoma, absence of a family history, normal thyroid hormone levels in family members, and the presence of an elevated glycoprotein α-subunit in patients with pituitary tumor. Reference: H Adams and D Adams. A case of a co-secreting TSH and growth hormone pituitary adenoma presenting with a thyroid nodule. EDM case reports 2018 Hatem.eid1@nhs.net
MON-680 Might Podocyturia Be an Early Marker for Diabetic Nephropathy in Males
Authors: Durcan Emre , Korkmaz Ozge Polat , Murt Ahmet , Saygi Halil Ibrahim , Sahin Serdar , Dincer Tamer , Ozkan Serbay , Bakir Alev , Ozkaya Hande Mefkure , Trabulus Sinan , Meydanli Emine Elif Guzel , Seyahi Nurhan , Gonen Mustafa Sait
Published: May 2020

Renal involvement can develop before detection of microalbuminuria in type 2 diabetes. There is an interest in finding biomarkers to detect diabetic nephropathy (DN) earlier and identify progression risk. Podocyturia emerge as a marker for early kidney damage however standardization problems hamper its widespread use. We aimed to investigate the value of podocyturia for the detection of early DN. Herein we report our preliminary results.

Our study population was composed of three type 2 diabetic patient groups and a healthy control group. Diabetic groups were defined as follows; group 1: patients without microalbuminuria who had HbA1c <7%; group 2: patients without microalbuminuria who had HbA1c> 8.5%; group 3: patients with diabetic retinopathy who had proteinuria >1g/day and/or microalbuminuria >300 mg/day and group 4: healthy volunteers without any known disease. Patients with glomerular filtration rate (GFR) below 30 ml/min were excluded.

GFR was calculated using the abbreviated MDRD formula. Microalbuminuria was measured in 24 hour urine. Number of podocytes in the urine was determined by immunocytochemical staining of podocalyxin. Due to the known expression of podocalyxin in the female genital tract, only males were included. Statistical analyses were carried out using Statistical Package for the Social Sciences version (SPSS) 24.0 and statistical significance was set as p<0.05.

We examined a total of 119 patients (mean age 57.35 ± 12.75 yrs.). Patient distribution in each group was as follows; group 1: 24(20%); group 2: 26(22%); group 3: 24(20%) and group 4: 45(38%) patients. There was no significant difference in mean age (p=0.582) and duration of diabetes (p=0.517) between the diabetic groups. The mean GFR was significantly lower in group 3 than in group 1 and 2 (p<0.001, p:0.007; respectively). The median podocyte measurement in urine was 0,25 (IQR: 0- 2.68) podx/ml in group 1; 0,37 (IQR: 0-2.12) podx/ml in group 2; 1,37 (IQR: 0.56-5.18) podx/ml in group 3; 0.0 (IQR: 0-0.75) podx/ml in group 4. The mean number of podocytes in urine was significantly different between the 4 groups (p=0.001). In posthoc analysis with Bonferoni correction, the mean podocytes measurement was significantly higher in group 3 than in group 1 and 4 (p=0.033, p=0.001; respectively).

According to our preliminary results; podocyturia assessed by podocalyxin immunostaining does not seem to be increased in male diabetic patients without proteinuria. Further studies on larger patient groups and using different podocyte markers might clarify the value of podocyturia as an early marker of DN.
SAT-346 Hypercalcemia Secondary to Calcitriol and PTHrP Cosecretion Only Responsive to Hydroxychloroquine
Authors: Panvelker Samir S , Khan Amna Nabeel
Published: May 2020

Background: Hypercalcemia of malignancy mediated by concurrent elevations in both 1,25-dihydroxyvitamin D (calcitriol) and parathyroid hormone (PTH)-related protein (PTHrP) is a rare phenomenon previously only reported with solid tumors. The preferred treatment for calcitriol-mediated hypercalcemia is glucocorticoid therapy and second-line therapy is traditionally ketoconazole. Hydroxychloroquine has previously been reported as efficacious only in cases of calcitriol excess related to sarcoidosis.

Clinical case: A sixty-two year-old female with a history of diffuse large B cell lymphoma, complicated by disease progression despite multiple treatment regimens over the preceding five years, developed acute hypercalcemia to a corrected value of 14.7 mg/dL (8.9-10.3). Work-up revealed a suppressed PTH, PTHrP <2.0 pmol/L (0.0-3.4), and calcitriol elevation of 136.0 pg/mL (19.9-79.3). She was treated with zolendronate with rapid normalization of calcium levels. Upon recurrence of hypercalcemia six months later, repeat calcitriol was 176.0 pg/mL with a new PTHrP elevation of 7.0 pmol/L. Repeat dosing of zolendronate was less efficacious. She was prescribed prednisone 60 mg daily with subsequent addition of denosumab 120 mg weekly with continued hypercalcemia. Given rising levels of calcitriol and PTHrP (up to 285.6 pg/mL and 43.5 pmol/L, respectively) and potential drug interactions between ketoconazole and her chemotherapy, she was started on hydroxychloroquine 400 mg daily. Her calcium normalized and calcitriol dropped to 61.1 pg/mL despite imaging evidence of continued lymphoma progression. Three weeks later, she developed septic shock and was transitioned to hospice.

Conclusion: In reviewing the literature, this appears to be the first reported case of a hematologic malignancy with pathologic levels of both calcitriol and PTHrP. It is also the first reported efficacy of hydroxychloroquine in malignant hypercalcemia. Interestingly, PTHrP secretion occurred months after the initial development of hypercalcemia. Control of both calcitriol and calcium levels did not occur until initiation of hydroxychloroquine despite preceding use of high-dose glucocorticoids and anti-resorptive therapy. Our case suggests that hydroxychloroquine should be considered in cases of calcitriol-mediated hypercalcemia resistant to glucocorticoids, particularly as it has less drug interactions and a more favorable side effect profile when compared to ketoconazole.
SAT-233 Primary Adrenal Diffuse Large B-Cell Lymphoma in HIV Patient: A Rare Case Report
Authors: Ibrahim Safa , Thibodeaux Rachel , Mathew Mini
Published: May 2020

Introduction: Primary adrenal lymphoma is remarkably rare type of extra-nodal lymphomas, accounting for <1% of non-Hodgkin lymphomas. For unclear reasons, HIV population appear to have an increased risk of developing non-Hodgkin lymphoma. We are presenting a rare case of bilateral primary adrenal non-Hodgkin lymphoma in HIV patient.

Case Presentation: A 65-year-old man with history of HIV, presents with nausea and generalized weakness for the past month. Other symptoms include, fever and unintentional weight loss of 10 kg also reported.

On admission, patient was found to have low sodium value of 124 mmol/L. He was worked up for hyponatremia; Labs were suggestive of primary adrenal insufficiency. Other endocrinology labs including; TSH, metanephrines, renin, and aldosterone were within normal values.

CT of the abdomen showed bilateral adrenal masses. The right lesion measured 10.6 cm. The left lesion measured 10.1 cm. Fungal work up was negative. Epstein Barr virus (EBV) panel was suggestive of convalescent versus reactivated disease.

CT guided biopsy of the adrenal mass confirmed Diffuse Large B-cell Lymphoma, activated B Cell Phenotype. Bone marrow biopsy showed no evidence of lymphoma.

Following oncology recommendations, patient was started on R-CHOP therapy. Currently, patient received two cycles of chemotherapy which he is tolerating well.

Discussion: Primary adrenal lymphoma is a rare type of non-Hodgkin lymphomas (NHL). Diffuse large B cell lymphoma (DLBCL) is the most common histologic subtype of NHL that present in the adrenal glands. Approximately one hundred cases reported of primary adrenal DLBCL in the literature with only two previously reported cases in HIV patients. It is considered an AIDS defining malignancy. HIV population are at higher risk of developing NHL than general population. The pathogenesis of the development of NHL in adrenal glands, which lack lymphoid tissue, particularly in HIV patients is yet to be determined, but impaired cellular immunity and chronic B cell stimulation and T cell immunodeficiency leading to loss of control of transforming viruses, particularly EBV are thought to play essential roles.

Because of the rarity of this tumor, diagnosis can be challenging. As exemplified in our patient, most cases have nonspecific presentation, including; fever, weight loss, night sweats, nausea, vomiting, adrenal insufficiency, and hyprecalcemia.

The recommended treatment for primary adrenal DLBCL is chemotherapy, with R-CHOP being the typical treatment. This disease appears to have a poor prognosis, and the median survival is approximately 1 year. Young age, good performance status, and early diagnosis and treatment can improve the outcome.

Conclusion: Primary adrenal DLBCL are rare tumors that has been associated in the literature with impaired cellular immunity. Our patient is the third case reported of primary adrenal DLBCL in HIV positive patient.
MON-669 Diabetic Macular Edema Thickness in Asians and Caucasians: Is There a Difference?
Authors: Leung Brian , Wu Gloria , Luu Shannon , Momen Donia , Lau Chap-Kay K
Published: May 2020

Background: Diabetic macular edema (DME) is a manifestation of diabetic retinopathy (DR) which can result in vision loss. DME affects over 750,000 US adults over the age of 40, costing 33% more in Medicare dollars than those patients without DME. Ethnicity plays a role in the development of DR but there are no studies about DME and HbA1c in Asians versus Caucasians. As Asians are the fastest growing ethnic group in the US and are at an increased risk of developing Type 2 Diabetes Mellitus (T2DM), there is a need for more knowledge about DME compared to Caucasians.

Purpose: Evaluation of diabetic macular edema thickness between Asian and Caucasian Diabetic patients.

Methods: A retrospective chart review (2017-2019) of consecutive diabetic patients were performed at California Retina Clinic. Inclusion criteria: DME thickness was measured by Optical Coherence Tomography (OCT) (Heidelberg Spectralis, Heidelberg, Germany), OCT +/- 3 months of their HbA1c lab test, control (C) non-diabetic patients=HbA1c <6.0%; For T2DM patients diagnosed by primary care physician: HbA1c ≥6.0%. Exclusion criteria: Age under 18 or over 90 years. Data analysis: R Project version 3.6.1 (R Foundation for Statistical Computing, Vienna, Austria). Two-way ANOVA was used to determine the difference between the four groups. The post-hoc test, Tukey’s HSD was used for p-values (<0.05).

Results: Of 500 consecutive patients: 80 patients met inclusion criteria: T2DM Asian (ADM), T2DM Caucasian (CDM), C Asian (CA), C Caucasian (CC). n=80 pts, avg age=59.187 years (sd=15.42, range 23-89 years), Female=44, Male=36;

ADM: n=20, avg age=60.90 years (sd=11.22, range 37-79 years), Female=10,Male=10, HbA1c range = 6.7-11.9%, Avg HbA1c = 7.59%, Avg DME=276.28 um (sd=25.93 um, range = 238.5-342 um);

CDM: n=20, avg age=68.05 years (sd=10.54, range 46-87 years), Female=9, Male=11, HbA1c range = 6.0-11.5%, Avg HbA1c = 7.52%, Avg DME=298.68 um (sd=33.84 um, range = 253.5-397.5 um); HbA1c in ADM v CDM: p=0.8(ns)

CA: n=20, avg age=52.85 years (sd=16.81 years, range 34-84 years), Female=10, Male=10, HbA1c range = 4.8-5.5%; Avg DME=267.05 um (sd=21.09 um, range = 230-310 um).

CC: n=20, avg age=62.95 years (sd=13.47 years, range 40-89 years), Female=14, Male=6, HbA1c range = 4.8-5.6%, Avg DME=285.68 um (sd=16.58 um, range = 248.5-312.0 um).

ADM v CDM and DME [F(1, 76)=13.267, p = 0.00049]. Tukey’s HSD post hoc tests were carried out. CDM v ADM had a significantly higher avg DME: 22.4 um (p=0.031). Body Mass Index (BMI): ADM patients (avg= 25.6) compared to CDM patients (28.5):(p=0.05, t-test).

Conclusion: In this small study, T2DM Asians had less macular edema thickness than T2DM Caucasians with similar HbA1c. T2DM Asian patients had lower Body Mass Index than T2DM Caucasians. Body Mass Index may be an additional factor to consider in the evaluation of diabetic macular edema in Asians and Caucasian Diabetic patients.
SUN-511 Thyroid Storm Caused by Subacute Thyroiditis in a Patient with Methicillin-Resistant Staphylococcus Aureus Septicemia
Authors: Assaad Mansur , Zuhdi Bisher , Groubert Jordan , Al-Shoha Ahmad
Published: May 2020

Introduction:

Thyroid storm is a rare disorder with high mortality risk. It is often precipitated by an acute event in a patient with longstanding untreated hyperthyroidism. However, thyroid storm is rarely reported as a result of subacute thyroiditis (SAT). To the best of our knowledge, there are only three documented cases of thyroid storm caused by SAT. Herein we report the first patient with thyroid storm caused by SAT associated with methicillin-resistant Staphylococcus aureus (MRSA) septicemia and intravenous drug abuse (IVDA).

Case:

A 19-year old Caucasian woman with a history of IVDA presented with right upper extremity abscess. Symptoms included confusion, agitation, fever, chills, generalized pain, malaise, nausea, and vomiting. Heart rate was over 140, and she was found to have fever and leukocytosis. She was admitted with severe sepsis and acute encephalopathy. On exam, she had a diffusely enlarged and exquisitely tender thyroid gland without discrete nodules or bruit. Thyroid tests were consistent with primary thyrotoxicosis (TSH 0.026 IU/mL, free T3 16.90 pg/mL, and free T4 > 6.99 ng/dL). Burch-Wartofsky score was 75, highly suggestive of thyroid storm. In addition to treating her sepsis, the patient was started on a beta blocker, high dose hydrocortisone, and methimazole. Thyroid ultrasound showed a diffusely enlarged heterogeneous thyroid gland with decreased flow on color Doppler. Upon improvement, the patient admitted to symptoms of anterior neck pain, heat intolerance, palpitations, excessive sweating, and anxiety for two days prior to presentation. Blood cultures later grew MRSA. Methimazole was discontinued when the thyrotropin-receptor antibody result came back negative. The patient continued to improve clinically. Her thyroid tenderness improved, and her free T4 and T3 decreased over a 3-week period. Steroids were tapered off.

Discussion:

SAT usually causes mild to moderate thyrotoxicosis. It is unusual for SAT to cause thyroid storm. Identifying such a diagnosis in a patient with sepsis is complex. In a septic patient, it is crucial to obtain detailed history, perform a comprehensive physical exam (including neck exam), and have a high level of clinical suspicion for thyroid storm in order to reach the diagnosis early and institute appropriate interventions. Establishing the underlying etiology of the thyrotoxicosis would have long term implications regarding prognosis and treatment.

References:

Salih AM, Kakamad FH, Rawezh QS, et al. Subacute thyroiditis causing thyrotoxic crisis; a case report with literature review. Int J Surg Case Rep. 2017;33:112-114.

Swinburne JL, Kreisman SH. A rare case of subacute thyroiditis causing thyroid storm. Thyroid. 2007;17(1):73-6.

Sherman SI, Simonson L, Ladenson PW. Clinical and socioeconomic predispositions to complicated thyrotoxicosis: a predictable and preventable syndrome?. Am J Med. 1996;101(2):192-8.
MON-203 Aldosterone Biosynthesis Among Patients with Overt or Subclinical Cushing’s Syndrome
Authors: Inoue Kosuke , Omura Masao , Hirfumi Horikoshi , Tsurutani Yuya , Saito Jun , Nishikawa Tetsuo
Published: May 2020

Background: Hypertension is one of the most common and distinguishing clinical features of patients with overt Cushing’s syndrome (CS) and subclinical Cushing’s syndrome (SCS). Although hypertension can be triggered by excess cortisol levels, it is unclear whether the cortisol is sufficient to explain the hypertension among these diseases (particularly SCS in which cortisol is slightly elevated) indicating the potential contribution of aldosterone to the elevated blood pressure. In this study, we aimed to examine the aldosterone biosynthesis among patients with CS or SCS.

Methods: We conducted the prospective study enrolling 90 patients (21 CS and 69 SCS) from 2016 to 2019 at Yokohama Rosai Hospital. We diagnosed patients with CS when they showed clinical features of CS and serum cortisol levels (F) after 1 mg dexamethasone (1-mg DST) was >5 μg/dl. SCS was defined as F after 1-mg DST was >1.8 μg/dl. For patients who are considered to be appropriate for adrenalectomy, we performed the segment-selective ACTH-loading adrenal venous sampling (AVS) to find the laterality of cortisol producing adenoma (CPA). The resolution of hypertension was assessed 1-year after the adrenalectomy.

Results: The median [interquartile range] age was 51 [46–62] years and males were 28%. Hypertension was observed in 21 (100%) CS and 58 (84%) SCS patients. Median F after 1mg-DST were 16.4 [14.3–18.7] mg/dl and 5.1 [3.4–7.5] mg/dl among CS and SCS patients, respectively. Median plasma renin activity among CS and SCS patients were 0.7 [0.4–1.3] ng/ml/h and 0.5 [0.2–0.9] ng/ml/h, respectively. Median plasma aldosterone concentrations (PAC) among CS and SCS patients were 8.3 [7.2–9.8] ng/dl and 9.3 [7.2–17.0] ng/dl at baseline, rising to 24.7 [18.6–32.3] ng/dl and 32.9 [25.8–48.3] ng/dl after ACTH stimulation. During the AVS, all SCS cases with hypertension showed the aldosterone excess (i.e. effluent aldosterone concentrations ≥1400 ng/dl after ACTH stimulation) in at least one adrenal segmental tributary vein. All CS cases showed the hypertension resolution after the resection of CPA except one case showing aldosterone excess on the opposite side of CPA. Among 39 SCS cases who underwent adrenalectomy, hypertension remained in 10 cases, and all of them showed aldosterone excess on the opposite side of CPA.

Conclusion: We found that aldosterone was likely to be elevated (or hyper-responsive to ACTH) among CS or SCS patients with hypertension. The proportion of the hypertension resolution after the CPA resection was lower when patients showed aldosterone excess on the opposite side of CPA. These findings indicate that elevated aldosterone may contribute to the high prevalence of hypertension and its resolution rate after adrenalectomy for patients with CPA. Further studies are needed to examine the clinical effectiveness of the intervention targeting aldosterone among patients with CS and SCS.
SUN-074 Loss-Of-Function Mutations in GATA4 in Patients with 46,XY Disorders of Sex Development Without Cardiac Defects
Authors: Lee Yena , Oh Arum , Yoo Han-Wook , Choi Jin-Ho
Published: May 2020

Background: Disorders of sex development (DSD) encompass a wide range of conditions associated with numerous causative genes. In about 50-60% of 46,XY DSD individuals, the underlying molecular cause remains uncertain. GATA4 haploinsufficiency has been described in patients with congenital heart defects (CHD), while only a few studies reported mutations related to 46,XY DSD phenotype. This study investigated clinical phenotypes and molecular characteristics of two 46,XY DSD patients with GATA4 mutations. Methods: Mutation analysis was performed in patients with 46,XY DSD by whole exome sequencing (WES) using Illumina NextSeq platform. Clinical and endocrine characteristics were reviewed retrospectively. GATA4 variants identified by WES were verified by Sanger sequencing. Functional activity of GATA4 variants was tested by luciferase reporter assay on the SRY and AMH promoter using two different cell systems including HEK293 and NCI-H295R. Results: Subject 1 presented with micropenis and hypospadias at the age of 5 months. Karyotype was 46,XY. Mullerian duct remnants were not found in pelvic ultrasound. The patient underwent urethroplasty at the age of 10 months and was reared as a male. Subject 2 with complete female external genitalia was referred to our hospital because of 46,XY karyotype on G-scanning. The patient underwent laparoscopic orchiectomy at the age of 1.8 years and was assigned as a female. Both patients were responsive to hCG stimulation tests and did not have CHD. Subject 1 harbored a novel heterozygous variant of c.643A>G (p.R215G)] in GATA4, whereas a previously reported variant of c.1220C>A (p.P407Q) was identified in Subject 2. In vitro luciferase reporter assays using SRY and AMH promoter revealed decreased transcriptional activity of both p.P407Q and p.R215G. Conclusions: This study expanded phenotypic spectrum of mutations in GATA4 in patients with 46,XY DSD without CHD. GATA4 mutations in patients with 46,XY DSD may not be associated with CHD. Possible explanations for phenotypical variability comprise incomplete penetrance, variable expressivity, and oligogenic mechanisms.
MON-096 Endocrine Complications Following Cancer Treatment in Survivors of Pediatric Solid Tumors: 18 Years’ Experience of a Single Academic Center
Authors: Lee Yena , Oh Arum , Choi Jin-Ho , Yoo Han-Wook
Published: May 2020

Background: Survival rates of pediatric cancer have been significantly improved over recent decades because of advances in chemotherapy and radiotherapy. The endocrine consequences of cancer treatment have become the major medical issues in the childhood cancer survivors. This study was performed to investigate the long-term endocrine complications in survivors of pediatric solid tumors. Methods: From 2000 to 2018, 402 patients were diagnosed with solid tumors including hepatoblastoma (n = 72), neuroblastoma (n = 117), Wilms tumor (n = 57), Ewing sarcoma (n = 40), osteosarcoma (n = 65), and rhabdomyosarcoma (n = 51) in our institute. Among them, 96 patients (24%) were expired during the follow-up period. Growth profiles and endocrinologic findings were analyzed by retrospective chart review in 306 survivors of solid tumors. Results: The median age at diagnosis of primary cancer was 3 years (range, 0 month to 18 years). The mean treatment duration was 11.7 ± 12.6 months, and the mean follow-up duration after cancer treatment was 7.1 ± 4.8 years. Short stature,which was defined by height-SDS below -2.0, was found in 39 patients (12.7%) with the mean height-SDS of -2.59 ± 0.45. Primary hypothyroidism was detected in 19 patients (6.2%), and 15 of them were treated with radiotherapy or 131I-MIBG therapy due to the metastatic neuroblastoma. Sixteen patients (5.2%) developed hypergonadotropic hypogonadism, whereas three patients (1%) were diagnosed with central precocious puberty. Vitamin D deficiency and osteoporosis were found in 4 patients (1.3%) and 3 patients (1%), respectively. Primary adrenal insufficiency was found in one patient who underwent bilateral adrenalectomy because of bilateral neuroblastoma. One patient with rhabdomyosarcoma in the nasal cavity underwent high dose radiotherapy (50.4 Gy) around the tumor site, eventually leading to multiple pituitary hormone deficiency. In multivariable analysis, longer duration of treatment (≥24 months) was associated with the endocrine complications (OR = 3.94; CI 1.41-11.06) and hematopoietic stem cell transplantation was a major risk factor for endocrine complications (OR = 4.70; CI 2.14-10.29). Conclusions: Various endocrine complications can occur in survivors of solid tumors in children and adolescents caused by treatment modalities including surgery, chemotherapy, and radiotherapy, rather than the tumor itself. Lifetime monitoring is necessary to detect endocrine consequences such as growth retardation, hypergonadotropic hypogonadism, and thyroid dysfunctions.