bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-060 Steroid Hormone Profile Differentiates Gynecomastia and Pseudo- Gynecomastia in Pubertal Boys
Authors: Reinehr Thomas , Kulle Alexandra , Barth Andre , Lass Nina , Holterhus Paul-Martin 
Published: May 2020

Abstract
Background: Gynecomastia (defined by breast tissue) and pseudogynecomastia (defined by adipose tissue) is frequent in pubertal boys. However, the underlying pathomechanisms are not fully understood so far. An association to growth hormone axis- IGF-1 axis and sex hormones has been discussed. Methods: We analyzed serum steroid hormones (progesterone, estradiol [E2], estriol, estrone, cortisol, cortisone, testosterone [T], dihydrotestosterone [DHT]) by liquid chromatography-tandem mass spectrometry, as well as gonadotropins, prolactin, IGF-1 and IGFBP-3 in 124 pubertal boys with breast swelling (mean age 14 +/-2 years). The steroid hormones were compared to those of 84 healthy pubertal boys (mean age 14 +/-2 years) without breast swelling. The differential diagnosis of either gynecomastia or pseudogynecomastia was determined by ultrasound. Puberty was defined by testes volumes &gt; 3ml on each side. Results: A total of 86 boys suffered from gynecomastia and 38 from pseudogynecomastia. In boys with gynecomastia the ratio E2/T (median 22, interquartile range [IQR] 8–75) was significantly (p&lt;0.05) higher compared to boys with pseudogynecomastia (median 12 IQR 5–21) or healthy boys without breast swelling (median 18 IQR 6–44). DHT concentrations were significantly (p&lt;0.001) lower in boys with gynecomastia (median 0.13 IQR 0.02–0.38 nM/L) or pseudogynecomastia (median 0.18 IQR 0.05–0.32 nM/L) compared to healthy boys (median 0.41 IQR 0.22–0.66 nM/L). T concentrations were significantly (p&lt;0.05) lower in boys with gynecomastia (median 1.8 IQR 0.7–4.2 nM/L) compared to boys with pseudogynecomastia (median 4.3 IQR 1.4–6.9 nM/L) or healthy boys without breast swelling (median 3.1 IQR 0.6–7.6 nM/L). The ratio DHT/T was significantly (p&lt;0.001) lower in boys with gynecomastia (median 0.09 IQR 0.02–0.17) or pseudogynecomastia (median 0.04 IQR 0.02–0.16) compared to healthy Boys without breast swelling (median 0.13 IQR 0.05–0.28). Boys with gynecomastia did not differ from boys with pseudogynecomastia according to the other steroid hormones, prolactin, IGF-1, or IGFBP-3 concentrations. Conclusions: Gynecomastia is characterized by a higher E2 to T ratio compared to healthy boys without breast swelling due to a relative T deficiency in the presence of similar E2 levels. The lower DHT/T ratio in gynecomastia and pseudogynecomastia compared to healthy boys without breast swelling points towards a functional 5 alpha reductase deficiency.
MON-127 Gaps in Knowledge of Social Determinants of Health in an Endocrinology Fellowship
Authors: Malek Rana , Lamos Elizabeth 
Published: May 2020

Abstract
Background: In June 2018, the Accreditation Council for Graduate Medical Education (ACGME) revised the common program requirements and identified a core requirement “to understand the social determinants of health (SDH) of the populations they serve and incorporate them in the design and implementation of the program curriculum, with the ultimate goal of addressing these needs and health disparities.1” Trainees must “demonstrate an awareness of and responsiveness to the larger context and system of health care, including the SDH, as well as the ability to call effectively on other resources to provide optimal health care.” While Association of American Medical Colleges (AAMC) teaching hospitals comprise 5% of the total US hospitals, they provide 40% of charity care in the US. In this setting, trainees need to be aware of the challenges faced by the communities they serve. SDH are increasingly recognized for their importance in the care of patients with diabetes and explain the health disparities in diabetes that exist throughout the US. Endocrinology fellows and the faculty teaching them must therefore demonstrate knowledge of SDH and health disparities.
Methods: We investigated the knowledge gaps in SDH in an urban academic endocrinology fellowship. All fellows and faculty members completed a 10-question survey that assessed knowledge, confidence, and motivation to learn about SDH. Six fellows and 10 faculty members completed the survey.
Results: While 60% of faculty and 83% fellows reported having an understanding of SDH, no fellows or faculty could correctly identify all 6 SDH. When asked about their confidence level in identifying SDH, 20% of faculty had low confidence, 70% were confident, and 10% were very confident. For fellows, 50% reported low confidence, 33% were confident, and 17% were very confident. There was lower confidence level in fellows and faculty when addressing SDH—with half the faculty feeling not confident or only somewhat confident. Fellows had lower confidence levels with addressing SDH, with 83% reporting low confidence. However, motivation was high amongst fellows and faculty to learn more about SDH—83% of fellows and 70% of faculty were very motivated to learn more about SDH.
Conclusion: The ACGME has made knowledge of SDH a common program requirement of all training programs. A needs assessment of SDH in an urban endocrinology fellowship program identified knowledge and confidence gaps about SDH, but a high motivation to learn by both fellows and faculty. While trainees and faculty often learn “on the job” about SDH and health disparities, this study reveals that formal curricular activities must be incorporated into endocrinology fellowship programs to meet the ACGME common program requirements.
1.
ACGME “Common Program Requirements.” https://www.acgme.org/What-We-Do/Accreditation/Common-Program-Requirements.
MON-015 Pregnancy Adapts Circadian Rhythms in the Reproductive Axis: Impact on Labor Regulating Drug Efficacy
Authors: Hoffmann Hanne Mette , Duong Thu V , Nguyen Duong , Muhammed Asad , Yaw Alexandra M 
Published: May 2020

Abstract
Molecular and behavioral timekeeping is regulated by the circadian system represented on the cellular level by clock transcription factors, including Period2 (PER2), Bmal1, Clock and Cry. These transcription factors drive a daily ~24h rhythm in gene expression leading to tissue specific receptor expression optimizing sensitivity to hormones and drugs dependent on the time of day. To synchronize circadian rhythms in the body to the time of day, the brain’s suprachiasmatic nucleus (SCN) translates environmental light information into neuronal and endocrine signals allowing circadian rhythm synchrony. Despite the critical role of circadian rhythms in fertility, it remains unknown how circadian rhythms change within reproductive tissues during pregnancy, and how these adaptations might impact drug efficacy. Monitoring wheel-running patterns in circadian PER2::luciferase (PER2::LUC) reporter mice, we confirmed that pregnancy is associated with reductions of activity and identified a correlation between delayed onset of behavioral activity during late pregnancy and ex vivo SCN PER2::LUC period, whereas no correlation between arcuate nucleus PER2::LUC rhythms was identified. The time of day of peak PER2::LUC expression provides a time-stamp as to the circadian phase of a tissue. Pregnancy impacted circadian synchrony in the reproductive axis, with the most dramatic change within the uterus. To understand how circadian rhythms responded to input during pregnancy, we performed a pharmacology study and found that circadian rhythm generation in the uterus responded differentially to hormones regulating pregnancy and labor depending on gestational age and the time of day of drug administration. To test for functional changes in uterine contraction capacity, we recorded ex vivo uterine contractions. Our preliminary data reveal a circadian change in uterine function in the mouse, which impacted labor regulating drug efficacy depending on the time of day. Together our data show that pregnancy is associated with behavioral changes in locomotor activity patterns, as well as adaptations in phase-relationships in reproductive tissues. Our chrono-pharmacology study indicates that a better understanding of labor-regulating drug efficacy can potentially allow increased efficacy of currently used drugs in the clinic to both induce labor as well as halt preterm labor.
MON-128 Improving Medication Adherence in Pediatric Patients
Authors: Diramerian Linda Garabet , Ejaz Sehar 
Published: May 2020

Abstract
Introduction Caring for chronic pediatric endocrine disorders commonly require long-term use of pharmacotherapy. Although these medications are effective in combating disease, their real benefits are often not achieved because of non-adherence. Health care professionals must be aware to the high prevalence of noncompliance which contributes to increased morbidity and medical complications, poorer quality of life and an overuse of the health care system and increase health care costs. Methods In order to better understand the factors contributing to noncompliance in our patient population, we performed a cross -sectional study along with medical chart review. We randomly selected 30 endocrine charts with chronic disorders and reviewed documentation of the need for medications, type of the visit, dose, duration, plan, patient compliance and refill follow up. Special attention was made if the physicians documented discussing the possible side-effects of the medication. An anonymous survey was handed to the parents at the end of visit and form was dropped in a locked box. No personal information or identification was collected. Parents were inquired about their understanding of the need for medication, side effects, compliance and the reason for poor compliance if they met the criteria. The chart reviewed showed that 47% of the patients reported poor compliance to physician during visit but when asked during the survey only 22 % reported poor compliance. 58% of the patients reported not knowing the possible side-effects of the medications. Reasons for non-compliance given by patients were 58% concerned about side effects of medication, refill not provided 4.8%, forgetting to take medication 2.4%, cost 2.4%, and language barrier 2.4%. Other 30% didn’t provide a specific reason for poor compliance. Conclusion Rates of medication adherence in pediatric patient with chronic medical illness range from 11% to 93%, with an estimated average of around 50%. Our population compliance correlates with the national average for pediatric population compliance. Our study also highlighted the importance of discussing possible side-effects with patients. Reviewing it periodically during clinic visits may decrease the risk of non-compliance. 58% of our patients reported lack of knowledge of proper side-effects of the treatment and impact of non -compliance to disease progression. Based on these results, we provided additional resources to physicians to better screen for factors that may affect compliance in each visit. Certain hard stops were added in medical documents and modifications were done in EMR. Information about common endocrine conditions and medication was added in EMR in English and Spanish. Physicians were encouraged to given written information about the proper use and side-effects. We are planning to do a follow up survey in 3–4 months to evaluate the improvement.
SUN-035 A Role for GNRH-II in the Control of Puberty?
Authors: Urbanski Henryk F 
Published: May 2020

Abstract
Hypothalamic gonadotropin-releasing hormone (GnRH) neurons represent the primary neuroendocrine link between the brain and the reproductive system. Although they play a key role in stimulating the release of FSH and LH from the anterior pituitary gland, the underlying mechanism by which they trigger the onset of puberty is unclear. To address this issue, RT-PCR, in situ hybridization histochemistry, and Affymetrix gene arrays were used to profile hypothalamic GnRH gene expression in prepubertal and adult rhesus macaques (Macaca mulatta). Like humans, these nonhuman primates express two molecular forms of GnRH (GnRH-I and GnRH-II), both of which are highly effective at stimulating gonadotropin release via the same GnRHR1 receptor. However, only GnRH-II shows increased hypothalamic expression in the presence of elevated estrogen concentrations (i.e., positive feedback), whereas GnRH-I expression either remains the same or decreases (i.e., negative feedback). In the present study, the hypothalamic expression levels of GnRH-I and GnRHR1 were found to be no different between prepubertal and adult animals, despite marked differences in circulating sex-steroid hormone levels, whereas the hypothalamic expression level of GnRH-II was significantly higher in the adults than in the juveniles. Therefore, although the traditional GnRH-I neurons are likely to play a fundamental role in initiating FSH and LH release during the early stages of pubertal development, GnRH-II neurons may play an important role in maintaining elevated gonadotropin release during the final stages (i.e., at a time when the GnRH-I neurons are subjected to increasing negative sex-steroid feedback from the maturing gonads). Taken together, the data suggest that sexual maturation in primates is likely to be orchestrated by the concerted action of two distinct GnRH neuronal subtypes that respond differentially to sex-steroid feedback.
SAT-363 Renal Papillary Necrosis Associated with Normocalcemic Hyperparathyroidism
Authors: Shakir Mohamed K M , Kiran Vijay , Bloomer Zachary , Shin Terry , Mai Vinh Q , Hoang Thanh Duc 
Published: May 2020

Abstract
IntroductionHypercalciuria is generally considered to be the most common identifiable metabolic risk factor for calcium nephrolithiasis. Important renal manifestations of primary hyperparathyroidism (PHPT) include asymptomatic nephrolithiasis, hypercalciuria, nephrocalcinosis, and chronic renal insufficiency. However renal papillary necrosis (RPN) occurring in PHPT has not been reported previously. We report a 50-year-old woman who manifested RPN associated with hypercalciuria and normocalcemic PHPT. Case ReportA 50-year-old Caucasian woman was evaluated in 2006 for hypercalcemia. She had no history of nephrolithiasis, fractures, or symptoms of hypercalcemia. Laboratory: serum calcium 11.8 mg/dL, ionized calcium 6.3 mg/dL, phosphorus 1.8 mg/dL, intact PTH 98 pg/mL (ref 15–65), urine calcium 543 mg/24 hrs (ref &lt;235). Renal ultrasound showed no evidence of nephrocalcinosis or nephrolithiasis. A parathyroid scan was consistent with a left superior parathyroid adenoma. Patient underwent parathyroidectomy and became normocalcemic with normal serum PTH levels postoperatively. One year later she was diagnosed with a left sided bronchial carcinoid tumor. Surveillance Gallium-68 PET/CT scan done 2 years later was negative for any metastases. Twelve years later she reported to our clinic for follow up. She had no symptoms of hypercalcemia, fractures, nephrolithiasis, history of pyelonephritis, diabetes mellitus, analgesic use, or hypertension. Serum calcium was 9.1 mg/dL, serum phosphorous 3.8mg/dL, PTH 82 pg/mL, 25-OH vitamin D 34 ng/mL, 1,25-vitamin D 38 pg/mL, and a urorisk panel was normal except for a 24-hour urine calcium of 410 mg. However renal ultrasound showed bilateral RPN and this diagnosis was also confirmed by a CT scan. A urinalysis showed only microalbuminuria with no red cells. She had no history of any analgesic drug abuse, pyelonephritis, sickle cell disease, or diabetes mellitus. A glucose tolerance test was completely normal. Discussion RPN is characterized by coagulative necrosis of the renal medullary pyramids and papillae brought on by several associated disorders and toxins that exhibit synergism toward the development of ischemia. Although the initial kidney US was normal, a repeat US done 12 years later showed evidence of RPN. This finding along with hypercalciuria and a diagnosis of normocalcemic PHPT suggests that RPN may be associated with hypercalciuria and normocalcemic PHPT. Furthermore she had no other risk factors for RPN. Additional studies with large number of patients are needed to confirm the association between these 2 disorders.
SAT-349 Cinacalcet Resistant Tertiary Hyperparathyroidism with One Large Parathyroid Gland
Authors: Chaker Bayan , Alim Hussam , Taha Wael 
Published: May 2020

Abstract
Tertiary hyperparathyroidism is thought to develop after long term secondary hyperparathyroidism, such as CKD on dialysis. In This case, all parathyroid glands are significantly enlarged.
We report a case of an 84-year-old female with a past medical history of ESRD on HD and recurrent nephrolithiasis who was found to have an enlarged multinodular goiter with the dominant mass in the lower pole of the right gland measuring about 4.7 cm on thyroid ultrasound. Blood work was done which showed elevated intact PTH levels at 2720 pg/mL (12–88). Her calcium level was normal at that time at 10.5 mg/dL (8.6–10.8) with an albumin of 4.2 g/dL (3.5–5.7), and a phosphorus of 5.7 mg/dL (2.5–4.5). Patient had a DEXA scan which showed severe osteoporosis in the lumbar spine, left hip, and right forearm. Patient had increased PTH levels despite being on Cinacalcet. She had a nuclear medicine parathyroid scan with SPECT CT which showed increased uptake along the right inferior thyroid concerning for a large right lower parathyroid adenoma or functional thyroid nodule. FNA of the nodule was done and showed colloid nodule but PTH wash showed elevated PTH at 7634 pg/mL. She was referred for right lower parathyroidectomy and Cinacalcet was discontinued prior to surgery. She had right and left inferior parathyroidectomy and 4 gland exploration. Pathology showed the right inferior parathyroid gland to be markedly hyper-cellular, weighing 36 grams consistent with hyperplasia and the left inferior parathyroid gland to be slightly hyper-cellular parathyroid gland consistent with hyperplasia. No evidence of malignancy was noted on pathology. Prior to surgery her calcium level of 10.6 mg/dL which went down to 9.6 mg/dL post-operatively. Patient then developed severe hypocalcemia and hungry bone syndrome following the surgery requiring a calcium drip for 3 days post-operatively. Was changed to oral calcium but required large amounts of calcium gluconate and calcitriol supplementation and an extended hospital stay of 13 days. However, throughout the hospital stay, PTH levels continued trending back up to 239 which may represent either increased activity from remaining parathyroid glands or residual parathyroid adenoma with incomplete resection. Post-operative US neck showed Post-surgical collection in the lower pole of the right gland measuring 4.8 cm compatible with recent resection.
In conclusion, tertiary hyperparathyroidism can develop due to one enlarged parathyroid gland or an adenoma, which can be resistant to cinacalcet.
MON-465 Novel Thyroid Hormone β Mutation L266s Causes Atrial Fibrillation & Cerebral Infarction
Authors: Ono Wataru , Kameda Hiraku , Iesaka Hiroshi , Izumihara Satomi , Oe Yuki , Kamigaki Risa , Chiba Koki , Kameda Rena , Nomoto Hiroshi , Cho Kyu Yong , Nakamura Akinobu , hayashi Yoshitaka , Hideaki Miyoshi , Atsumi Tatsuya 
Published: May 2020

Abstract
Background: Resistance against thyroid hormone β (RTHβ) is characterized by reduced tissue sensitivity to thyroid hormone. Patients with RTHβ resistance typically demonstrate increases in FT3 and FT4 accompanied by inappropriately elevated TSH. Mutations in the TRβ gene are the most common genetic disorder in thyroid hormone resistance and result in impaired thyroid receptor functions due to a dominant negative effect. Here, we describe a case with a novel TRβ mutation, presenting atrial fibrillation and cerebral infarction.
Clinical case: A 55-year-old man presented chronic atrial fibrillation and tachycardia as the onset of cerebral infarction. Because blood tests revealed 5.6 pg/ml FT3 (reference range: 2.36–4.06), 3.39 ng/ml FT4 (0.71–1.5), 0.98 TSH μIU/ml (0.541–4.261), and negative TRAb, suggesting inappropriate secretion of TSH (SITSH). He was referred to our department for further investigation. All three test kits, including LUMIPULSE, ECLusys, and TOSOH, showed an unsuppressed TSH value despite hyperthyroxinemia, demonstrating genuine SITSH. His family history was unclear, but his father had died of heart disease. A pituitary MRI suggested microadenoma, but TSH-secreting pituitary adenoma was excluded because of a negative α subunit and responsiveness to a TRH stimulation test. The TRβ gene was analyzed with informed consent from the patient, and a novel mutation replacing the 266th amino acid serine (TCG) with leucine (TTG) in the 8th exon was found, confirming the diagnosis of RTHβ. Tachycardia and atrial fibrillation were considered to be caused by thyrotoxicosis in heart, which dominantly expresses TRα rather than TRβ. Therefore, β-blockers and anticoagulants, were continued.
Conclusion: This is the first report of a case of RTHβ with the TRβ L266S mutation. This novel mutation is located in the thyroid hormone-binding area of the TRβ gene, suggesting that reduced hormone binding may cause thyroid hormone resistance.
SAT-674 Anti PD1 Induced Type 1 Diabetes
Authors: Naranjo Maria Belen , Rosenthal David S , Kumar Salini Chellappan , Shariff Amal 
Published: May 2020

Abstract
Introduction: Pembrolizumab t is used to treat various cancers. It is associated with immune related adverse events (IRAEs) that can be life threatening [1,4]. We describe a patient who presented autoimmune Diabetes after the use of Pembrolizumab. Case: 64 y/o African American female PMHX of lung non-small cell lung cancer diagnosed in 2017 Clinical stage IV with gluteal metastasis, and dementia. Pt was referred by Oncology. The patient had a family history of Type 1 DM. and complained of dizziness, and unintentional weight loss (30 pounds) over a year. She had received 2 cycles of Pembrolizumab. The last cycle given 5 weeks before presentation to Endocrinology.Physical examination revealed cachectic female (weight 35 kg, height 147cm), dry mouth, BP 135/82, Plasma glucose 383mg%, A1c 7, negative Islet cell antibodies, positive anti-GAD, undetectableserum C-peptide. Cortisol 27, Acth 21 at 8 am and TSH 2.3. Discussion: In a systematic literature review, the early pattern of Diabetes onset with the use of checkpoint inhibitors was evaluated and on average after 4.5 treatment cycles [4].The incidence of immune checkpoint inhibitor-induced Type 1 Diabetes is estimated at 1% [3].This appeared to be earlier for the combination of anti-cytotoxic T-Lymphocyte associated antigen 4 monoclonal antibody and PD-1 therapy. The onset of β cell inflammation is often fulminant, suggested by the relatively low glycated hemoglobin levels, while C-peptide levels are usually low or undetectable at diagnosis and mostly positive GAD antibodies [5]. This side effect is predominantly found in patients exposed to blockade of the PD-1/PD-Ligand pathway. The IRAEs are primarily managed by immunosuppression with corticosteroids and discontinuation of immunotherapy except in autoimmune Diabetes which is irreversible. Physicians should be aware of and patients educated about the important multiorgan side effects since a growing number of patients are treated with checkpoint blockade.Azoury SC, Straughan DM, Shukla V. Immune checkpoint inhibitors for cancer therapy: clinical efficacy and safety. Curr Cancer Drug Targets 2015;15: 452-462Weber JS, Postow M, Lao CD, et al. Management of adverse events following treatment with anti-programmed death-1 agents. Oncologist 2016;21:1230-40Stamatouli AM, Quandt Z, Perdigoto AL, Clark PL, Kluger H,Weiss SA et al Collateral damage: insulin-dependent diabetes induced with checkpoint inhibitors. Diabetes 2018;67(8):1471-1480de Filette JMK, Pen JJ, Decoster L, et al. Immune checkpoint inhibitors and Type 1 Diabetes mellitus: a case report and systematic review. Eur J Endocrinol. 2019;181(3):363–374.Akturk HK, Kahramangil D, Sarwal A, Hoffecker L, Murad MH, Michels AW. Immune checkpoint inhibitor-induced Type 1 Diabetes: a systematic review and meta-analysis. Diabet Med. 2019;36(9):1075–1081.