bluuebunny/crossref_metadata_2025_split huggingface dataset:
OR30-02 Efficacy and Safety Comparison Between U100 Regular Human Insulin and U100 Rapid Acting Insulin When Delivered by a 24 Hour Wearable Insulin Delivery Device in Type 2 Diabetes
Authors: Mora Pablo , Sutton David R , Gore Ashwini , Baliga Bantwal S , Goldfaden, PharmD Rebecca , Nikkel Carla , Sink II John , Adams-Huet Beverley 
Published: May 2020

Abstract
Introduction: Increasing insulin prices have led to a renewed debate to determine if Rapid Acting Insulin (RAI) analogs offer an advantage over less expensive Regular Human Insulins (RHI). The steep increase in the cost of RAI has led to rationing of insulin or the total discontinuance of therapy by many patients due to cost. For many, RHI provides a more affordable option for insulin therapy when compared to RAI, especially if the limitations of the insulin profile can be overcome by delivering RHI through continuous subcutaneous insulin infusion (CSII) using a wearable insulin delivery device. To our knowledge, no data exists in a type 2 diabetes (T2D) population comparing RAI to RHI when delivered via CSII. Methods: This 14 week multi-center prospective, randomized parallel, non-inferiority study in a T2D population compared the efficacy and safety of RAI versus RHI when delivered by V-Go®, a 24-hr wearable patch-like insulin delivery device that provides a preset continuous basal rate of insulin and on-demand bolus dosing. This study was conducted in a real-world practice setting under usual standard of care. Glucose lowering agents were to remain stable unless removal warranted due to documented clinically significant hypoglycemia and the only specific guidance for insulin titration was to down-titrate if blood glucose levels were consistently lower than target range. Patients administering RAI with V-Go were randomized 1:1 to continue RAI or to switch to RHI. Primary endpoint assessed non-inferiority for the between group net difference in HbA1c derived from a mixed model analysis. Between group differences from baseline for insulin total daily dose (TDD) and hypoglycemia (based on 7 point glucose profiles) were evaluated as secondary endpoints. Results: One hundred thirteen patients (59 RHI and 54 RAI) were evaluated. Baseline characteristics were similar between cohorts. The mean change in HbA1c with RHI was -0.60% from a baseline of 8.41% vs -0.38% from a baseline of 8.33% with RAI (estimated treatment difference [ETD]: -0.22%; 95% confidence interval [CI] -0.67% to 0.22%; non-inferiority margin&lt;0.4% and p=0.007). The mean change in TDD with RHI was 0.8 U/day from a baseline of 61.0 U/day vs 1.8 U/day from a baseline of 61.3 U/day with RAI (ETD: -1.04 U/day; 95% CI: -3.18 U/day to 1.11 U/day; p=0.92). The absolute change in percent of patients reporting hypoglycemia (≤ 70 mg/dL) from pre-randomization to post-randomization was +5.08% with RHI vs + 5.56% with RAI (ETD: -0.48%; 95% CI: -10.6% to 9.1%; p=0.91). Severe hypoglycemia was not reported in either cohort. Conclusion: Patients with T2D administering RAI with V-Go can safely switch to RHI maintaining similar glycemic control.
SAT-037 Effect of Weight on Serum Testosterone with Subcutaneous Testosterone Enanthate in Men with Testosterone Deficiency
Authors: Bhattacharya Rajib , Tursi James P , Jaffe Jonathan S 
Published: May 2020

Abstract
BACKGROUND: In men, obesity is often associated with low testosterone (T) levels, but information is limited as to how body weight affects the pharmacokinetic profile or dosing of testosterone therapy (TTh) in men with T deficiency. Historically, men with body mass index (BMI) &gt;32.4 kg/m2 required higher doses of T 2% gel to achieve physiological T levels than men with BMI ≤29.1 or 29.2–32.4 kg/m2.(1) In a phase 3 trial (N=150) of subcutaneous (SC) testosterone enanthate (TE) administered weekly, concentration-guided dosing raised T levels to within physiological range in 92.7% of patients.(2) Here, we report a post hoc analysis evaluating the association between body weight and serum T levels attained with SC TE. Methods: SC TE was evaluated in an open-label, single-arm, dose-blinded, 52-week phase 3 trial (NCT02159469). Patients self-administered 75 mg SC TE weekly during the titration phase; blinded dose-adjustments in 25 mg increments occurred at pre-defined time points beyond the sixth dose. The primary endpoint of this study was the percentage of patients achieving an average serum T concentration (Cavg0-168h) of 300 to 1,100 ng/dL at week 12. For this post hoc analysis, a linear regression model with weight and dose as independent variables was used to assess differences in mean minimum T concentration (Cmin) and Cavg0-168h at week 12. Results: For this analysis, 137 patients were included. Doses were 50 mg (n=25), 75 mg (n=93), and 100 mg (n=19). The mean weight was 84.4 kg, 102.2 kg, and 112.0 kg for the 50 mg, 75 mg, and 100 mg dose groups, respectively (range, 49.9–146.5 kg). The dose-normalized T Cmin was 9.2 ng/dL, 5.7 ng/dL, and 4.3 ng/dL per 1 mg of SC TE for the 50 mg, 75 mg, and 100 mg groups, respectively. The dose-normalized T Cavg0-168h was 12.0 ng/dL, 7.2 ng/dL, and 5.7 ng/dL per 1 mg of SC TE. In an overall linear regression model, 48.2% (P&lt;0.0001) and 55.0% (P&lt;0.0001) of the total variance in Cmin and Cavg0-168h, respectively, can be predicted from the independent weight and dose variables. Conclusion: Our results show an inverse relationship between body weight and T exposure. Men with higher mean body weights required higher doses of SC TE to achieve physiologic T levels compared with men with lower mean body weights. The available doses provide effective options to reach target exposures. These findings highlight the impact of weight and dose selection on SC TE exposure. References: (1) Dobs et al., J Sex Med 2014;11:857–864; (2) Kaminetsky et al., J Urol. 2019;201:587–94.
SUN-265 Reduced Locomotive Behaviour and Increased Arcuate Nucleus Inflammation Are Observed in KISS1R KO Male Mice
Authors: Patel Raj , Maloney Shane K , Smith Jeremy Troy 
Published: May 2020

Abstract
The neuropeptide kisspeptin, encoded by the Kiss1 gene, binds the G- protein-coupled receptor Kiss1r (also known as GPR54) and is a novel player in the delicate balance of energy intake and expenditure. Mice that have a dysfunctional gene for Kiss1r develop an obese and diabetic phenotype. To further study how kisspeptin signalling impacts on energy balance, we investigated the relationship between absent kisspeptin signalling and locomotor behaviour in Kiss1rKO and wild type mice. Mice had free access to running wheels, and we examined the characteristics of wheel running over three weeks, and its flow-on effects on body mass. We subsequently examined dopaminergic neurons (via tyrosine hydroxylase (TH) staining) and hypothalamic inflammation (via Iba1 stained microglia). These studies also were performed following gonadectomy (GDX), to control for gonadal steroids. In intact males, the knockout (KO) mice covered only 10% of the distance travelled by wild-type (WT) per 24h (WT, 6363±643m; KO, 652±219m; P&lt;0.0001). Moreover, in the WT there was a clear circadian pattern to the wheel-running activity, with most activity during lights off, while in the KO the running appeared randomly distributed across the 24h. After GDX, KO males continued to run significantly less than their WT counterparts (WT, 1652±474m; KO, 998±219m). In intact females, the KO mice covered only 23% of the distance travelled by WT per 24h (WT, 6030±747m; KO, 1379±364m; P&lt;0.004). In OVX females, there was no difference between WT and KO mice (WT, 4150±1367m; KO, 3117±830m). Bodyweight analysis showed that access to running wheels prevented obesity usually seen in the Kiss1rKO mouse. In fact, in GDX males and females (at days 21 and 22 of wheel running) the KO mice were significantly lighter than WTs (at day 22: males, WT 28.67g; KO, 23.70g; P&lt;0.05; females, WT, 27.38g; KO, 23.30g; P&lt;0.05). Examination of TH revealed no significant difference in expression in the different genotypes in both sexes, in all areas examined. Investigation of Iba1 revealed significant higher counts in the male KO compared to the WT in the arcuate nucleus, but no difference in any other regions. We show that the locomotor activity in male and female Kiss1r KO mice is heavily dependent on the status of gonadal sex steroids. However, the lower running activity in male KO compared to WT remained after GDX, and this was paired with an elevated inflammation marker in the arcuate nucleus. Whether absent kisspeptin signalling acts as a significant regulator of voluntary activity is debatable, but patterns of locomotion behaviour could be disrupted, potentially involving circadian rhythm, this is under further investigation.
OR04-06 G Protein GSα in Muscle Is Essential for Survival During Cold Adaptation in the Absence of Thermogenesis of Brown Adipose Tissue
Authors: Chen Min , Sun Hui , Weinstein Lee Scott 
Published: May 2020

Abstract
Adaptive thermogenesis is important for the control of body temperature (Tb) and maintenance of body weight, and it is primarily regulated by sympathetically-driven brown adipose tissue (BAT). Studies indicate that muscle is also involved in thermogenic regulation. Gsα couples to ligands and receptors, including β-adrenergic receptors, to increase intracellular cAMP. Our previous studies have showed that mice with adipose-specific Gsα deficiency had inactive BAT and impaired cold tolerance. To determine whether Gsα/cAMP signaling in skeletal muscle compensates for loss of BAT thermogenesis, we generated mice with Gsα deficiency in adipocyte tissue alone (AdipGsKO), in skeletal muscle alone (SkMGsKO) or in both (AdipSkMGsKO). Compared to control mice, AdipGsKO and SkMGsKO mice had normal body weight, while AdipSkMGsKO showed reduced body weight with normal food intake and energy expenditure. Both AdipGsKO and AdipSkMGsKO mice had elevated fasting glucose levels, but similar glucose tolerance to control or SkMGsKO mice. SkMGsKO mice displayed reduced insulin sensitivity. When acutely exposed to 6oC for 3 hours, AdipGsKO and AdipSkMGsKO mice rapidly decreased their Tb, indicating that they are sensitive to acute cold exposure, consistent with their inactive BAT. To assess adaptation to chronic cold, mice were exposed to gradually declining ambient temperature from 22oC to 6oC with a daily decrease of 2oC and were then kept at 6oC for 5 days. As expected, both AdipGsKO and AdipSkMGsKO mice failed to stimulate BAT UCP1 by cold adaptation. Unexpectedly, AdipGsKO mice maintained normal Tb similar to control and SkMGsKO mice. However, AdipSkMGsKO mice started to rapidly drop their Tb when ambient temperature declined to 14oC and 85% of SkMGsKO mice (11/13) died before the end of experiment. These results suggest that when there is a lack of BAT function, Gsα/cAMP signaling in muscle plays an essential role for mice to survive in response to chronic cold challenge.
SUN-285 Too Big to Be True, Too Young to Stroke!
Authors: Jalil Fatima , De La Portilla Lori , Lorenzo Joseph Anthony , Mirza Faryal Sardar 
Published: May 2020

Abstract
BACKGROUND: Lactotroph adenomas are the most common type of pituitary adenomas and can cause infertility and menstrual irregularities in women; hypogonadism and gynecomastia in men.1 Giant prolactinomas are an unusual subset of pituitary macroadenomas with limited literature available on their management.2 We describe an unusual case of giant prolactinoma in a young man who presented with symptoms of stroke, that reversed with treatment with cabergoline. Clinical Case: 25-year old man presented with gradually progressing upper extremity weakness for evaluation of stroke. He reported stumbling into things when walking. There was a question of left sided facial droop and Bell’s palsy in recent past. He reported recent weight gain and erectile dysfunction. He was noted to have left homonymous hemianopsia on exam in addition to left upper and lower extremity weakness. MRI Brain showed an enormous mass that filled the sella turcica, invaded the sphenoid sinus and right side of the skull base, invaginating deep into the base of the right cerebral hemisphere with mass effect on the pons, right-sided midbrain, right temporal lobe and right basal nuclei, measuring 6.3 X 5.5 x 7.5 cm. Pituitary hormonal evaluation showed elevated prolactin (PRL) level with dilution at 13,580 ng/mL, with low testosterone (T) level (total T 42 ng/dL, free T 10 pg/mL, SHBG 15 nmol/L). Thyroid and adrenal axes were intact with normal IGF-1 level. In view of very high PRL level, he was started on cabergoline 0.5 mg daily initially and decreased to every other day after 2 weeks as PRL level began to decline. In 8 months, PRL levels decreased to 1293.07 ng/dl (90% reduction) and prolactinoma decreased to 6.0 x 3.7 x 4.7 cm (56% volume reduction). Total and free T improved to 134 ng/dL and 31 pg/dL respectively. He experienced marked improvement in left hemianopsia, with resolution of weakness and slurred speech. Energy level and erectile dysfunction improved. Currently he is being maintained on 0.5 mg cabergoline every other day Conclusion: Giant prolactinomas are uncommon and can present with compressive symptoms, that can be mistaken as stroke. Treatment with anticoagulation may cause hemorrhage and apoplexy with worsening of symptoms.1,2 There is limited data available regarding first line therapy for giant prolactinomas with 2 case reports where giant prolactinomas have been treated effectively with cabergoline.3,4 It is important to recognize the cause of such symptoms, and treated where possible with effective medical therapy to prevent morbidity. References: 1. Moraes A et al., Giant prolactinomas: the therapeutic approach. Clin Endo (Oxf). 2013 Oct;79(4):447-56 2. Acharya SV et al., Giant prolactinoma and effectiveness of medical management. Endocr Pract. 2010 Feb;16(1):42-6 3. Ahmed, M, et al., Large Prolactinoma. NEJM 2010; 363:177 4. Masoud, R et al., Giant prolactinoma: case report. J Diabetes Metab Disord. 2013; 12: 3
SUN-098 Low-Dose Infigratinib Treatment Does Not Lead to Changes in Phosphorous Preclinically in Mice
Authors: Reyes Maribel , Sinha Uma , Li Gary , Martin David 
Published: May 2020

Abstract
BACKGROUND: Infigratinib (BGJ398) is a potent and selective FGFR1-3 inhibitor under evaluation for the treatment of achondroplasia, the most common form of disproportionate short stature. Low doses of infigratinib were shown to be effective in improving skeletal abnormalities in a mouse model of achondroplasia [Demuynck et al. 2019; Komla-Ebri et al. 2016]. At higher doses in adult patients (e.g. 10-100-fold the dose shown to have efficacy in preclinical models of achondroplasia) infigratinib appears to be associated with elevation in phosphorus, an effect known to be associated with FGFR1 inhibition. Specifically, FGFR1 inhibition leads to decreases in FGF23, which, in turn, leads to decreased excretion of phosphate by the kidneys. We sought to understand the relationship between lower doses of infigratinib and changes in phosphorus in preclinical animal models. Methods: Changes in phosphorus were tested at multiple doses in three different species - mouse, rat, and dog - across five different studies. Infigratinib was given orally at doses ranging from 0.03 mg/kg to 30 mg/kg. Both PK and PD (i.e., phosphorus) data was available in all species. Measurement days ranged from day 10 to week 12, although PK/PD measurements occurred within 1 day of each other. All animals were treated in accordance with AVMA guidelines. Results: No significant dose-phosphorus relationship was observed in rats and mice treated with doses of infigratinib ranging from 0.03 mg/kg to 5 mg/kg. A dose-phosphorus and exposure (AUC0-24)-phosphorus relationship was observed at doses of infigratinib ≥10 mg/kg across transgenic mouse, rat, and dog studies. At low doses, the exposure (AUC0-24)-phosphorus relationship showed a shallow slope with linear regression analysis in rats and mice. Conclusions: These findings from five studies in three different species indicate that the exposure-phosphorus relationship is consistent. Importantly, no relationship was observed between dose and phosphorus levels in rats and mice treated with infigratinib at or below 5 mg/kg. Despite the fact that infigratinib is a FGFR1, 2 and 3 inhibitor, low doses of infigratinib shown previously to exert a significant effect in improving skeletal abnormalities in an achondroplasia mouse model, do not seem to result in meaningful changes in phosphorus. These experiments demonstrate that at doses of infigratinib much lower than used in oncology - like those being considered for use in clinical studies of achondroplasia - infigratinib is less likely to cause hyperphosphatemia. Infigratinib will be evaluated in global clinical studies in children with achondroplasia in 2020.
SAT-517 A Rare Case of Lithium-Induced Thyroiditis
Authors: Lokshin Vladimir , Soni Lina , Shrestha Sujata , Guber Helena Abby 
Published: May 2020

Abstract
BACKGROUND: Lithium is known to cause both hypo- and rarely hyper- thyroidism. It inhibits release of thyroid hormone and reduces the intrathyroidal iodothyronine/iodothyrosine ratio. Due to direct toxic or immunostimulatory effect, lithium can also cause thyroiditis. Lithium-induced thyroiditis is a rare entity with an incidence rate of about 1.3 cases per 1000 person-years. Given its generally painless and transient nature, symptoms of thyrotoxicosis may erroneously be attributed to an exacerbation of mania.
Clinical Case: We report the case of a 29 y/o man with bipolar disorder on lithium therapy who presented with a 2 week history of intermittent palpitations, increased irritability, racing thoughts, insomnia, tremors, increased bowel movement frequency, and 8 lbs weight loss despite an excellent appetite. He denied ocular symptoms, and did not have any recent illness, or new stressors. He had been on a stable dose of lithium for four years.
The physical exam was notable for: pulse 78 bpm and regular, exophthalmos, and a palpable, non-tender, non-nodular, thyroid. Labs: TSH 0.008 uIU/ml [0.350 - 5.50], FT3 6.5 pg/ml [2.0 - 4.4], T3 2.08 ng/mL [0.6–1.94] and FT4 1.96 ng/dl [0.8 - 2.7]. TPO, TSI and anti-thyroglobulin antibodies were negative. The lithium level was in the therapeutic range. Thyroid Uptake Scan showed decreased uptake of 2.6 % [normal 10–35%]. He was started on methimazole 20mg daily and atenolol, lithium was changed to risperidone by Psychiatry.
After 2 months, hyperthyroid symptoms had resolved, and he was biochemically hypothyroid (FT4 0.85 ng/dl, TSH 20uIU/ml). Methimazole and atenolol were discontinued, with sustained euthyroid state. Conclusion: Hyperthyroidism may develop after several years of lithium therapy. It may be mistaken for aggravation of mania, or for Grave’s disease, especially since lithium and Graves’ are both associated with exophthalmos. Key issues for management are whether to continue lithium and deciding if the incorporation of antithyroid medications is necessary. Of utmost importance is regular monitoring of thyroid function tests to ensure resolution of thyroiditis and to avoid the development of overt hypothyroidism.
SUN-058 Endocrine and Metabolic Complications in 16 Taiwanese Patients with Thalassaemia Major
Authors: Lo Fu-Sung 
Published: May 2020

Abstract
Backgrounds: Endocrine and metabolic abnormalities are quite common in patients with thalassaemia major, attributable, at least in part, to chronic iron overload. Endocrine and metabolic abnormalities are quite common in patients with thalassaemia major. Determining the prevalence of endocrine complications is difficult because of differences in the age of first exposure to chelation therapy, and the continuing improvement in survival in well-chelated patients.Patients and Methods: We performed a retrospective study of endocrine and metabolic data of 16 Taiwanese children (10 females and 6 males, 21.42±4.82 years) who attended in our patient clinics from Oct 2002 to Jan 2012. We analyzed height, weight, BMI, serum fasting glucose, thyroid function, growth hormone, adrenal, and gonadal functions. Results:These patients had very high serum ferritin levels with 4737.79±4572.03 ng/ml (482.8-12639). Auxological data show growth retardation (height SDS -1.05±1.34, weight SDS -0.67±0.52, BMI -0.37±0.49). Endocrine data reveal hypogonadism (n = 11, 69%), hypothyroidism (n=8, 50%), growth hormone deficiency (n=3, 19%), and adrenal insufficiency (n=3, 19%). Metabolic data show impaired fasting glucose (n=4, 25%) and diabetes (n=6, 37%). Conclusions: Patients with thalassemia major are at risk for a number of endocrine (growth hormone deficiency, hypothyroidism, adrenal insufficiency and hypogonadism) and metabolic problems (impaired fasting glucose and diabetes). It is necessary for endocrinologists to become skilled in these complications and provide long-term comprehensive care through the life of these patients.
MON-022 Dissecting the Interplay Between Diet and PCOS Pathology on Gut Microbiota in a PCOS Mouse Model
Authors: Paris Valentina Rodriguez , Kaakoush Nadeem O , Solon-Biet Samantha M , Edwards Melissa C , Ledger William L , Gilchrist Robert B , Simpson Stephen J , Handelsman David J , Walters Kirsty A 
Published: May 2020

Abstract
The gut microbiome has been implicated in the development of metabolic disorders such as obesity and type-2 diabetes, and more recently polycystic ovary syndrome (PCOS). PCOS is a heterogeneous disorder with reproductive, endocrine and metabolic irregularities, and clinical and animal studies have reported that PCOS causes a decrease in microbial diversity and composition. Diet is an important regulator of the gut microbiome, and a recent study identified that alterations in macronutrient balance impact gut microbial communities which correlate with different metabolic health outcomes (1). We have identified that macronutrient balance impacts the development of PCOS traits. Therefore, to investigate the interplay between macronutrient balance and a PCOS environment on the gut microbiome, we analyzed the intestinal microbiome from fecal pellets of control and DHT-induced PCOS mice exposed to 10 different diets that varied systematically in protein (P), carbohydrate (C) and fat (F) content. The amount of dietary P, C and F consumed significantly altered alpha and beta diversity of the gut microbiota of pooled control and PCOS mice (P&lt;0.0001). Alpha diversity between control and PCOS mice on the same diet did not differ significantly, and hence was only affected by diet composition. However, beta diversity was significantly altered between control and PCOS mice (P&lt;0.05). We performed DESeq2 analysis and identified an operational taxonomic unit (OTU) within Bacteroides (OTU3) to be the most differentially abundant OTU between control and PCOS mice, with a significant decrease in PCOS mice compared to controls (control: 7.88 and PCOS: 5.38; fold change = 1.464; P&lt;0.0001). The consensus sequence of Bacteroides OTU3 was found to share 99.2% similarity to Bacteroides acidifaciens. B. acidifaciens is associated with obesity with elevated levels reported to prevent the onset of obesity (2). Thus, we then investigated the influence of P, C and F on the relative abundance of Bacteroides OTU3 and revealed an association with C consumption, with increasing levels of C leading to increased levels of Bacteroides OTU3 (Carb: r= 0.22, p=0.0028, q=0.015). These findings demonstrate that diet exerts a stronger influence over the gut microbiome than PCOS pathology. However, the hyperandrogenic PCOS environment does lead to changes in gut microbiota beta diversity, with a specific decrease in an obesity-associated (2) Bacteroides species in PCOS mice that is also responsive to levels of C consumption. Reference: (1) Holmes et al., Cell Metabolism. 2017; 25(1): 140-151. (2) Yang et al., Mucosal Immunology. 2017, 10 (1), 104-116.