bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT-351 A Novel Mutation in the Calcium-Sensing Receptor Gene Presenting in a Kindred as Autosomal Dominant Familial Hypocalciuric Hypercalcemia
Authors: Bushman Jordan , Banka Ajaz 
Published: May 2020

Abstract
Rationale: Familial hypocalciuric hypercalcemia (FHH) is a benign cause of hypercalcemia. The majority of cases result from an inactivating mutation in the calcium-sensing receptor (CaSR). While affected patients are usually asymptomatic and require no treatment, this condition may go unrecognized and inappropriate parathyroidectomy for presumed primary hyperparathyroidism could be performed. Over 130 mutations in the CaSR gene have been reported and novel variants continue to emerge.
Methods: The initial patient was a 49 year-old female who presented with mild hypercalcemia, elevated PTH and undetectable urine calcium. She reported several of her family members had elevated calcium levels. Given high clinical suspicion for FHH genetic analysis was performed.
Results: Sequencing of the CaSR gene revealed a point mutation at c.1744T&gt;A which resulted in p.Cys582Ser in exon 7. This cystine residue is highly conserved and predictive algorithms suggest this variant is likely disruptive leading to heterozygous loss of function in the CaSR. The patient’s 26 year-old daughter was tested and found to have the same mutation.
Conclusion: We report the identification of a novel heterozygous mutation in the CaSR gene manifesting as FHH in a family of Iraqi decent. Additional family members are currently undergoing genetic analysis which will be included at the time of presentation.
MON-034 Impact of Race and Obstructive Sleep Apnea on Glucose and Insulin Regulation in Women with PCOS
Authors: Temple Karla A , Mokhlesi Babak , Carter Jason R , Whitmore Harry , Van Cauter Eve , Ehrmann David A 
Published: May 2020

Abstract
The prevalence of prediabetes and diabetes is substantially higher in PCOS women with obstructive sleep apnea (OSA) compared to PCOS women without OSA1,2,3. Prior studies, however, did not examine the complex interaction between race and OSA on metabolic function in PCOS. We sought to determine if the impact of OSA on glucose and insulin metabolism is affected by race. We studied non-Hispanic white (NHW) (n=53) and African-American (AA) (n=48) women with PCOS. Following an overnight polysomnogram (PSG), PCOS women (NHW without OSA n=40; NHW with OSA n=13; AA without OSA n=36; AA with OSA n=12) had a 2-h 75-g oral glucose tolerance test (OGTT) with blood sampling every 30 minutes for measurement of glucose, insulin, and C-peptide concentrations. OSA severity was measured by the Apnea-Hypopnea Index (AHI). Only women without OSA (AHI &lt; 5) or with moderate-to-severe OSA (AHI &gt; 15) were included in these analyses; women with mild OSA were excluded. Insulin secretion rates (ISR) during the OGTT were derived by deconvolution of C-peptide levels 4. Area under the curve (AUC) response to the glucose challenge was calculated using the trapezoidal method. BMI and age did not differ between races in PCOS women without OSA (BMI [kg/m2]: 36.3±1.2 vs. 37.2±1.1, p=0.58; Age [yr]: 27.7±0.8 vs. 27.2±0.8, p=0.65; for NHW and AA respectively), or in PCOS women with OSA (BMI [kg/m2]: 42.8±1.7 vs. 44.7±2.0, p=0.50; Age [yr]: 31.4±1.6 vs. 28.6±1.6, p=0.18; for NHW and AA respectively). OSA severity was similar in NHW and AA PCOS women without OSA (AHI: 1.5±0.2 vs 2.1±0.2, p=0.076), and PCOS women with OSA (AHI: 32.0±4.9 vs. 28.3±4.4, p=0.26). Higher glucose responses during the OGTT were observed in NHW PCOS women with OSA compared to both NHW (AUC: 18,965±648 vs. 15,797±371, p=0.0004) and AA (AUC: 18,965±648 vs. 15,801±497, p=0.0005) PCOS women without OSA. Glucose responses did not differ significantly between AA PCOS women with OSA and AA PCOS women without OSA (AUC: 17,104±965 vs. 15,801±497, p=0.15). Similarly, ISR was higher in NHW PCOS women with OSA compared to both NHW (AUC: 5,648±488 vs. 3,907±231, p=0.0006) and AA (AUC: 5,648±488 vs. 3,981±235, p=0.0011) PCOS women without OSA. ISR did not differ significantly between AA PCOS women with OSA and AA PCOS women without OSA (AUC: 4,827±461 vs. 3,981±235, p=0.09). CONCLUSIONS: OSA has a greater impact on glucose and ISR during an oral glucose challenge in NHW compared to AA women with PCOS. Future studies would benefit from including race when evaluating metabolic outcomes in women with PCOS. References: 1Fogel et al., J Clin Endocrinol Metab. 2001: 86:1175–1180. 2Kapsimalis et al., Sleep. 2002; 25:499–506. 3Kapsimalis et al., Sleep. 2002; 25:412–419. 4Polonsky et al., J Clin Invest. 1986 Jan; 77(1):98–105.
SAT-504 Delayed Hypersensitivity to Levothyroxine, and Oral Desensitization
Authors: Sandooja Rashi , Morocco Michael Dominic , Smith Martin 
Published: May 2020

Abstract
Introduction- Hypothyroidism is a common endocrine disorder, affecting about 4.6 percent of the U.S. population aged 12 and older. The most common treatment is synthetic thyroxine hormone supplementation-levothyroxine, starting at 1.6 mcg/kg.Hypersensitivity reactions to levothyroxine are rare. Two cases have been published of successful oral desensitization, for suspected IgE mediated reactions. There are no published protocols describing induction of drug tolerance to immunologic, non-IgE mediated reaction to levothyroxine. The objective of this case report is to describe a novel outpatient protocol, for oral desensitization to levothyroxine, in the setting of a delayed immunologic (non-IgE mediated) reaction.
Case report- A 66 year old male with history of hypothyroidism, diagnosed in 2010 presented to outpatient endocrinology. Between 2010 and 2019, the patient was on multiple brands and formulations of levothyroxine. He noticed an itchy, raised rash on abdomen, chest and arms, within a few months after starting each of the above. No mucosal involvement or signs of end organ damage were noted. The rash was deemed a type IV delayed hypersensitivity reaction, based on history and histological findings on biopsy. The patient reported clearance of the rash when he was off any form of thyroid supplementation, and reappearance of the rash when he re-trialed it. The patient had normal thyroid stimulating hormone (TSH) levels while he was on supplementation despite the rash. The patient’s TSH after discontinuing treatment was 104 (uIU/mL) and free thyroxine (T4) was 0.13 ng/dl (0.9–1.7). All components of previous brands of levothyroxine were compared and no common ingredient was thought to be contributing to hypersensitivity reactions. Subsequently, an oral desensitization protocol was initiated at 0.075 mcg daily with weekly increase in doses over seven weeks to reach a target dose of 75 mcg.
Discussion- The patient was tried on different brands of levothyroxine and dessicated thyroid hormone. He consistently developed a type IV hypersensitivity reaction within a few months after starting them. The patient had uncontrolled TSH levels after discontinuing the treatment and was at risk of complications of untreated hypothyroidism. This necessitated the need for desensitization. There have been previous case reports of oral or IV desensitization, in suspected IgE mediated reactions, but we describe the first case of induction of levothyroxine tolerance in an immunologic non-IgE mediated reaction. Subsequently, the patient tolerated a therapeutic dose of levothyroxine, with no appearance of rash or itching, for almost 6 months. This case report describes a novel approach to levothyroxine desensitization over a period of seven weeks in an outpatient setting in response to a delayed type hypersensitivity reaction.
SAT-001 Clinically Meaningful Effects of E2/P4 Oral Capsule in Treating Vasomotor Symptoms
Authors: Constantine Ginger , Graham Shelli , Revicki Dennis A , Kagan Risa , Mirkin Sebastian 
Published: May 2020

Abstract
Hormonal therapies effectively reduce the frequency and severity of vasomotor symptoms (VMS) in menopausal women; however, whether the effect is clinically meaningful to women is typically not determined. Oral estradiol/progesterone (E2/P4; mg/mg) 1/100 and 0.5/100 significantly improved moderate to severe VMS versus placebo at weeks 4 and 12. The objective of these analyses was to determine the clinical importance (meaningfulness) of E2/P4 treatment versus placebo in menopausal women.
REPLENISH, a phase 3, randomized, double-blind, placebo-controlled trial, evaluated the safety and efficacy of E2/P4 oral capsules in symptomatic, postmenopausal women with a uterus. Clinically meaningful reductions in weekly VMS frequency were determined using 3 patient-reported outcomes as anchors (VMS severity score, clinical global impression [CGI], and question 1 from the vasomotor domain of the menopause-specific quality of life questionnaire). The proportion of women who had a clinically important response with 0.5/100 was compared with placebo using the Fisher’s exact test. Spearman correlations were also performed across the 3 anchors.
Clinically meaningful reductions in weekly VMS frequency ranged from 32 to 43 at week 4, and from 32 to 48 at week 12. Significantly more responders were observed with 0.5/100 than with placebo for all 3 anchors at both weeks 4 (all, P&lt;0.05) and 12 (all, P≤0.002). All 3 anchors were correlated, supporting their acceptability as appropriate anchors.
Treatment with E2/P4 0.5/100 provided consistent clinically meaningful improvements in the weekly frequency of moderate to severe VMS in menopausal women, similar to what has been observed with the CGI-anchor for E2/P4 1/100.
SUN-368 Wnt Inhibition Decreases Trabecular Bone in a Mouse Model of Fibrous Dysplasia
Authors: Lung Hsuan , Wentworth Kelly , Moody Tania , Kang Misun , Ho Sunita , Hsiao Edward 
Published: May 2020

Abstract
Background: G protein-coupled receptor (GPCR) signaling mediates a wide spectrum of physiological functions, including bone development and remodeling. Fibrous dysplasia (FD) is a common skeletal dysplasia where normal bone and bone marrow are replaced by fibrous tissue and expansile trabecular bone lesions. The craniofacial bones are often involved, leading to pain and facial deformities. FD is a mosaic disease caused by a somatic mutation in the GNAS gene encoding the G-protein alpha subunit (Gsα) that leads to constitutive activation of the Gs signaling pathway. Unfortunately, FD has no effective medical treatments.
Major challenges have hampered the development of pharmacologic strategies that specifically target GNAS or the Gsα protein. We previously developed the Col1(2.3)/Rs1 mouse model (Rs1) in which the Gs signaling pathway is activated specifically in bone by an engineered GPCR protein. These mice showed increased trabecular bone formation with loss of marrow space and cortical bone, which strongly resembles human FD (1–4). There was also a dramatic increase in the number of immature osteoblasts present in the FD lesions, suggesting that activation of Gs signaling caused an accumulation of these cells. Our prior studies showed increased Wnt signaling, which may be a major driver of this effect. Furthermore, blocking the Gs signaling could reverse the bone phenotype, providing proof-of-concept for finding drugs that could reverse the phenotype. Therefore, we administered the Wnt inhibitor LGK974, currently used in human clinical trials, to the Rs1 mice to test if the FD lesions could be pharmacologically reversed.
Methods: We administered LGK974 in 4-week-old Rs1 and non-Rs1 mice. We used a low dose (5mg/kg) for 8 weeks or high dose (30mg/kg) for 4 weeks. The mice were evaluated by histology and micro computed tomography (micro-CT) for mineral density (mg/cm3), bone volume (mm3), and trabecular thickness (um).
Results: LGK974 decreased β-catenin levels in bone on western blots. In the low-dose group, the histology and micro-CT showed no statistically significant differences between drug and control groups. In the high-dose group, the micro-CT showed significantly decreased trabecular bone thickness (p=0.0364, n=3) in the drug-treated group (22±2µm) compared with controls (17±2µm). Furthermore, histology showed resorption of the abnormal bone; however, the fibrocellular infiltrate in the Rs1 mice was still present.
Conclusions: Wnt inhibition can lead to decreased fibrous dysplastic bone, but separates abnormal bone formation from the fibrocellular infiltrate. These results provide new insight into understanding interactions between the Wnt and Gs signaling pathways in FD pathogenesis and bone formation.
References: 1. Hsiao EC et al. PNAS. 2008. 2. Hsiao EC et al. JBMR. 2010. 3. Schepers, Hsiao EC et al. Blood. 2012. 4. Cain CJ et al. Endocrinology. 2016.
SUN-273 A Rare Case of IgG4-Related Hypophysitis
Authors: Ravindra Sindhura , Fazeli Pouneh 
Published: May 2020

Abstract
Introduction:
Hypophysitis is an acute or chronic inflammation of the pituitary gland and is an important diagnostic consideration in a patient with a sellar lesion. The annual incidence of hypophysitis is estimated to be 1 in 7–9 million and it accounts for approximately 0.4% of pituitary surgery cases. The following highlights a rare case of isolated IgG4-related hypophysitis
Clinical Case:
A 63-year-old Caucasian female presented with sudden onset of diplopia and decreased visual acuity. This was associated with a 3-month history of headaches and 5-lbs weight loss. Past medical history was significant for hypertension and a 1.5cm sellar/suprasellar mass incidentally discovered during the work-up for persistent headaches 1-month prior. Initial anterior pituitary hormone evaluation was normal and the patient was scheduled for endoscopic endonasal resection of a presumed non-functioning pituitary adenoma. Family history was negative for pituitary tumors or hyperparathyroidism. Physical examination was notable for medial deviation of her left eye but neurologic examination was otherwise normal. Laboratory studies were notable for a normal TSH [1.769 uIu/ml (normal: 0.3–5.0)] and low free T4 [0.44 ng/ml (normal: 0.89–1.78)] consistent with central hypothyroidism; an inappropriately normal FSH for a postmenopausal woman [5.6 mIu/ml (normal: 0.3–10.5), and a normal prolactin level [16 ng/ml (0.6–20)]. An 8am cortisol was low at 2mcg/dL (5–21) with an ACTH level of 10 pg/mL (9–46). IGF-1 was normal at 89 ng/mL (41–279). Repeat pituitary MRI imaging demonstrated a homogenously enhancing sellar/suprasellar mass measuring 3.8 cm with displacement of the optic chiasm. Serum IgG4 levels were normal. The patient was started on 50mg IV hydrocortisone every 8 hours for central adrenal insufficiency and levothyroxine 88 mcg daily for central hypothyroidism and underwent an endoscopic endonasal biopsy of the lesion. Surgical pathology was notable for plasma cell-rich lymphohistiocytic hypophysitis and IgG4 plasma cells constituted &gt;40% of the total plasma cell population. The patient subsequently received 1g of rituximab and repeat imaging one week later showed marked improvement in the size and extent of the lesion. The patient was discharged on prednisone and levothyroxine and received a second dose of rituximab at follow-up. The patient reports a decrease in the frequency of her headaches but continues to endorse diplopia.
Conclusion:
IgG4-related hypophysitis typically presents as part of a multifocal systemic process. This case highlights a rare entity of IgG4-related hypophysitis without other features of systemic disease and with normal serum levels of IgG4. Although glucocorticoids are universally regarded as the first line of therapy, an immunosuppressive agent or B-cell depletion therapy such as Rituximab may improve remission and decrease the risk of relapse.
MON-675 Ziprasidone Induced Diabetic Ketoacidosis
Authors: Thanikonda Varshitha , Jalil Fatima , Kantorovich Vitaly 
Published: May 2020

Abstract
Introduction: Atypical antipsychotics are known to cause increased risk of type 2 Diabetes Mellitus (DM2), dyslipidemia, and weight gain (metabolic syndrome). Clozapine, a commonly used anti-psychotic, is known to cause Diabetic Ketoacidosis (DKA), but literature has rarely shown an association of DKA with Ziprasidone.
Case: A 42-year-old African American female presented with two weeks of polyuria, polydipsia, 23-pound weight loss, blurriness of vision, and dry mouth. Before the presentation, she had been drinking several drinks with high sugar content. Her medications included Ziprasidone (Geodon), Trileptal, and Cogentin for her bipolar disorder. She was started on Ziprasidone in 2007, changed to Brand name Geodon in 2014. Except for dry mouth, her exam was unremarkable. Labs were significant for blood glucose of 1114 mg/dL, bicarbonate of 18mmol/L, beta-hydroxybutyrate of 3.33 mmol/L, serum osmolality of 334 mOsm/kg. She was diagnosed with new-onset diabetes mellitus presenting as diabetic ketoacidosis. Her mother was diagnosed with DM2 in her 40s. She ha difficult to control blood sugars despite aggressive hydration and required regular insulin drip for 3 days for her anion gap to close. Managing her BGs was challenging.
Discussion: Clozapine and olanzapine are the common atypical antipsychotics that can cause DKA1, 2. To our knowledge, Ziprasidone is associated with hyperglycemia within days of starting the drug and HHS but not with DKA. For atypical antipsychotic associated DKA, risk factors include the duration of antipsychotic therapy, polypharmacy with multiple antipsychotic agents, non-Caucasians, obesity and pre-diabetes2, 3. Proposed mechanisms include peripheral insulin resistance, alteration of pancreatic beta-cell function by inhibiting 5-HT1A/2A/2C and alpha 2 adrenergic receptors1-3. However, there is no explanation of why few people develop complications while others do not. There is hypothesis regarding leptin gene polymorphisms of receptors that may play a role4. While starting patients on Ziprasidone, close monitoring of blood glucose is necessary before initiation and regular follow up thereafter3.
1. Henderson DC. Atypical antipsychotic-induced diabetes mellitus: How strong is the evidence? CNS Drugs. 2002.
2. Vuk A. Diabetic ketoacidosis associated with antipsychotic drugs: Case reports and a review of literature. Psychiatr Danub. 2017.
3. Schwenkreis P. Atypical antipsychotics and diabetes mellitus. World J Biol Psychiatry. 2004.
4. 1. Reynolds GP. Metabolic side effects of antipsychotic drug treatment - pharmacological mechanisms. Pharmacol Ther. 2010.
SAT-686 Type 1 Diabetes Diagnosed in an 83 Year Old Man After Nivolumab Therapy
Authors: Joseph Marina , Borikar Madhura , Bursey Deborah I 
Published: May 2020

Abstract
BACKGROUND
Immune checkpoint inhibitors are increasingly being used for a variety of cancers and are a promising treatment option. Immune related adverse effects are their major side effects, most common being hypophysitis and hypothyroidism. While diabetes and adrenalitis have only been rarely reported, these too are becoming more common. We present a case of type 1 diabetes associated with Nivolumab therapy diagnosed in an 83-year-old man.
CASE
An 83 year old male with past medical history of emphysema, coronary artery disease, hypertension, non-small cell lung cancer treated with lobectomy, hepatitis C cirrhosis with hepatocellular carcinoma with metastasis to lungs, who completed 10 cycles of Nivolumab presented to oncology clinic with complains of polyuria, polydipsia and a weight loss of 10 pounds over the last one week. Lab work showed a blood glucose of 743 with an anion gap of 18 and bicarb of 18. B-hydroxy butyrate was 3.19. He was admitted to our ICU for diabetic ketoacidosis. He did not have a history of diabetes mellitus. No family history of diabetes was reported. His Hemoglobin A1c was found to be 10.1. He had normal blood sugars before starting Nivolumab therapy. His C-peptide was found to be low at 0.61. Insulin antibody, Islet cell antibody, Zinc transporter antibody and GAD antibodies were negative. He was discharged on basal bolus Insulin regimen. He is being followed in our endocrinology clinic and continues to be insulin dependent.
CONCLUSION
Nivolumab is PD-1 (programmed cell death) inhibitor, which is used as cancer immunotherapy in multiple advanced cancers including hepatocellular carcinoma. Clinically significant endocrinopathies are documented in &lt;5% of patients treated with PD-1 inhibitors. The cause of Diabetes by PD-1 inhibitors is not well defined but believed to be caused by destruction of pancreatic beta cells due to inhibition of autoimmunity by autoreactive T cells. Literature review showed only 42 published cases of PD-1 inhibitor induced type 1 diabetes. Average age at presentation was 62 years and about 69% patients were in DKA at diagnosis. In a recently published study involving 1163 patients who received PD-1 inhibitors, only 21 cases of diabetes were identified, 12 of those were with new onset DM and only 1 case was due to Nivolumab use.
Since this type of endocrinopathy is mainly reported in case reports, we will need more research for further understanding of the pathology so that we can keep a watch out for this adverse effect and prevent life- threatening complications.
SUN-719 The Impact of FOXA3 on Testicular Steroidogenesis
Authors: Kim Hansle , Kumar Sudeep , Lee Keesook 
Published: May 2020

Abstract
The Forkhead box(Fox) transcription factors are evolutionarily conserved in organisms and regulate diverse biological processes during development as well as adult life. Among the Fox family, FoxA subfamily members Foxa1-3 have been termed `pioneer’ transcription factors as they bind both nucleosome-bound and nucleosome-free DNA targets with the same recognition site. Foxa3 is the only member of FoxA subfamily that is expressed in both male and female gonads. In the testis, Foxa3 is expressed in spermatids and interstitial Leydig cells. We focused our study to elucidate the role of FOXA3 in Leydig cells and its impact on testicular steroidogenesis. Expression of FOXA3 dramatically decreased in mouse Leydig cells during testicular development. In addition, the time-dependent expression of FOXA3 showed an opposite pattern to that of steroidogenic genes in cAMP-induced primary Leydig cells. Meanwhile, Nur77 is among the prime regulators of steroidogenesis in the testicular Leydig cells. Overexpression of FOXA3 in MA-10 cells (mouse Leydig tumor cell line) repressed the cAMP-induced Nur77 promoter activity, which further resulted in the reduced activity of Nur77-target steroidogenic gene promoters (StAR, CYP17A1and 3β-HSD). Similar to above results, the expression of Nur77 and its target genes,StAR, 3β-HSD and CYP11A1, were repressed by adenovirus-mediated overexpression of FOXA3 in mouse primary Leydig cells, although the expression of CYP17A1, another steroidogenic gene, was differentially affected. These results suggest that FOXA3 locally regulates the expression of steroidogenic genes through Nur77 during testicular development.