bluuebunny/crossref_metadata_2025 huggingface dataset:
OR08-04 Differences in Advanced Lipoprotein Profile Between Rabson-Mendenhall Syndrome and Lipodystrophy
Authors: Al-Jundi Mohammad , Lightbourne Marissa , Startzell Megan , Shamburek Robert D , Brown Rebecca J
Published: May 2020

Insulin resistance (IR) is associated with metabolic dyslipidemia (high triglycerides [TG] and low HDL) and increased cardiovascular disease (CVD) risk. In obesity-associated IR, dyslipidemia is thought to be caused by increased insulin-mediated stimulation of hepatic lipogenesis, whereas IR in glucoregulatory pathways leads to hyperglycemia. This dichotomy in insulin signaling pathways is termed selective insulin resistance. Rare human conditions exist in which there is extreme, non-selective, IR impairing all insulin signaling pathways (e.g. mutations of the insulin receptor, INSR) or extreme IR affecting only selected intracellular insulin signaling pathways analogous to obesity (e.g. lipodystrophy). Lipodystrophy leads to very high TG, low HDL, and increased CVD, while INSR mutation leads to low TG and high HDL, with unknown CVD risk. We sought to further characterize the lipid phenotype and atherogenicity in these conditions in order to understand effects of different insulin signaling pathways on CVD risk.

We studied 7 patients with INSR mutation (42% female; 5 homozygous; 2 heterozygous) and 21 with lipodystrophy (85% female; 5 generalized; 16 partial). Fasting lipoprotein profiles were assessed by NMR using the LP4 deconvolution algorithm. The major lipoprotein particle categories defined by this method are small, medium, and large HDL and LDL particles (HDLP and LDLP) and very small, small, medium, large, and very large TG rich lipoprotein particles (TRLP).

Very small TRLP (median 189.6 [68.7, 315.0] vs 4.5 [0.00, 9.4], p=0.0001), small LDLP (mean 1425.0 ± 636.2 vs 612.8 ± 233.9, p=0.003), small HDLP (mean 14.0 ± 4.7 vs 9.0 ± 3.2, p=0.014) were more elevated in patients with lipodystrophy vs INSR mutation. This lipoprotein profile has been associated with increased atherosclerotic coronary artery disease. GlycA, a marker of inflammation was also more elevated in lipodystrophy vs INSR mutation (435.9 ± 107.2 vs 315.7 ± 74.4, p=0.01). Insulin resistance assessed by HOMA-IR was higher in patients with INSR mutation vs lipodystrophy (mean 93.5 ± 94.4 vs 15.6 ± 14.7, p=0. 00085).) Lipoprotein insulin resistance (LPIR), an index of IR based on lipoprotein particles, was lower in patients with INSR mutation (25.0 ± 19.0 vs 84.0 ± 9.0, p < 0.0001) despite their higher HOMA-IR.

In conclusion, severe, selective insulin resistance in patients with lipodystrophy was associated with a more atherogenic lipoprotein particle profile and increased inflammation compared to severe, non-selective insulin resistance caused by INSR mutations. Patients with INSR mutations had a striking discrepancy between a glucose/insulin-based index of insulin resistance (HOMA-IR) and a lipid-based marker of insulin resistance (LPIR). These findings point toward a key role of selective insulin resistance in the development of an atherogenic lipid profile, which should lead to increased CVD risk.
MON-337 Peripheral Neurological Complications in Pregnancy- Is Idiopathic Transient Osteoporosis of Pregnancy Concerning?
Authors: Aljaberi Asma Khaled , Szolics Miklos
Published: May 2020

Idiopathic transient osteoporosis of pregnancy (ITOP) is a rare and under-reported condition that has affected healthy pregnancies. ITOP usually presents in the final trimester of a normal pregnancy. Radiographic studies detect drastic loss of bone mass, elevated rates of turnover in the bone, and edema in the affected portion.

We present a 26-year-old previously healthy woman, who was admitted at 39 weeks of gestation with severe left hip pain and inability to walk for one month.The pain was constant, progressive, involving left lower limb, and associated with numbness and weakness. Neurological exam revealed diminished power in the left hip (motor power was 2/5), and inability to stand and walk due to pain in the left hip. She was unable to stand by herself. Investigations revealed anemia, low vitamin B12, low vitamin D and magnesium. Bilateral hip MRI showed increased T2WI signal in the left femoral head consistent with idiopathic transient osteoporosis of the left hip (ITOP). DXA scan showed bone mass density (BMD) below expected for age.The patient had induced vaginal labor without complication. The left hip pain improved after delivery. She was treated conservatively with Calcium, Magnesium and vitamin D. The patient symptoms completely resolved in 3 months post-delivery. DXA scan and Hip MRI at 1 year interval showed normal BMD and complete resolution of previous bone marrow edema and changes seen in MRI hip.

This case report serves to highlight the effect of pregnancy on bone mass during third trimester which may result in transient osteoporosis of pregnancy leading to weakness and gait disturbance. Clinical symptoms can be misdiagnosed as a peripheral neurological complications instead of bone metabolism changes of pregnancy.
MON-322 The Characteristic of Reproductive Disorders in Women with ACTH-Dependent Cushing Syndrome in the Republic of Uzbekistan (RUz) and Republic of Karakalpakstan (RKK)
Authors: Khalimova Zamira Yusufovna , Irgasheva Oydin Bahodirovna , Mirsaidova Umida Akmalovna , Jabborova Gavhar Muzravjanovna
Published: May 2020

The aim- to study the characteristic of the reproductive function in patients with ACTH-dependent Cushing Syndrome in (CS) in all regions of the RUz and RKK.

Material and methods. Under our supervision in the all regions of RUz and Tashkent-city there are 120 women of fertile age with ACTH-dependent Cushing Syndrome were observed in the framework of project. Middle age of patients was 27,6 ± 3, 4 years.

The complex of researches, including clinical, biochemical hormonal (ACTH, LH, FSH, cortizol, prolactin), ultrasound investigations, pituitary and adrenals CT/MRI was executed all patients.

Results. The patients were divided into 2 groups: 1 group - patients with conservative treatment - 47 cases (39,1%), 2 group -patients with pituitary surgery - 65 cases.(54,1%), 3 group - combined therapy - 8 patients (6,6%).

The reproductive disorders had 63 women from 120 (52,5%): amenorrhoea -35%), oligomenorrhoea (30%), polimenorrhoea (7,5%). It was found that with ACTH - dependent Cushing’s syndrome, primary infertility was 17,6%, secondary 23.5%,

We found hyperandrogenemiya and hypercortizolemiya in patients of all groups before treatment. Estradiol levels were significantly inversely correlated with cortisol levels. One year after surgery we established normal range of LH, FSH, ACTH, cortizol, prolactin in all women of 2 group, but in 1 and 3 group we didn’t achieve compensation yet.

After 1 year only 1 (2,1)% women from 1 group can pregnant. After 1 year 30 women from 65 patients of second group after pituitary surgery (46,1%) achieved pregnancy without stimulation therapy. There are 2 (25%) women of 3 group achieved pregnancy.

The restoration of reproductive function in women with CS was observed in 3,5% of cases in patients treated with medical therapy, 33,3% in patients with adrenalectomy and combination therapy, and 50% after transsphenoidal adenomectomy of pituitary tumor.

Conclusions. The fertility function in women with ACTH-dependent CS can improve after pituitary surgery without stimulation therapy. In 46,1% of cases, in patients with combined therapy -in 25%and in women after conservative therapy - in 2,1%.
SUN-078 Clinical, Hormonal, Psychosexual Aspects, Gonadal Tumors and Genetic Background of an Androgen Insensitivity Syndrome Cohort
Authors: Batista Rafael Loch , Ramos Raquel Martinez , Almeida Gomes Nathalia Lisboa Rosa , Ferrari Maria Tereza Martins , Elias Felipe Martins , Rodrigues Andresa De Santi , Nishi Mirian Yumie , Silva Juliana M , Costa Elaine Maria Frade , Domenice Sorahia , Mendonca Berenice Bilharinho
Published: May 2020

Introduction: Androgen Insensitivity Syndrome (AIS) is the most common cause of Differences of Sexual Development (DSD) in 46, XY individuals. It is a X-linked genetic disease caused by allelic variants in the Androgen Receptor Gene (Xq11-12), leading to 3 different phenotypes: Complete (CAIS), Partial (PAIS) or Mild (MAIS). Methods: Patients with clinical suspicion of AIS (familial history, atypical genitalia, primary amenorrhea and/or inguinal hernia) performed hormonal serum measurements (LH, FSH, estradiol, testosterone) and molecular sequencing of the ARgene, including all exonic regions (8 exons) and the 5’UTR region. Psychosexual variables (gender identity, gender role and sexual orientation) were evaluated through questionnaires. Gender identity was also evaluated through projective psychological test (HTP test). A histopathological study and immunostainining of CD240 and OCT3/4 were carried out for all individuals submitted to gonadectomy.Results: This cohort is made up of 64 individuals: CAIS (n=26) and PAIS (n=38), from 46 different families (24 PAIS; 22 CAIS). Inguinal hernia was the first clinical presentation in 35% of CAIS. Among the PAIS, 20 (52%) were assigned as female at birth, while 18 (48%) as male. Among In the group of PAIS, external genitalia virilization (Sinnecker score) influenced sex assignment (p<0.01). Final height and weight were similar between PAIS and CAIS. Furthermore, gender identity at adulthood, gender role at childhood and sexual orientation were in agreement with sex assignment in virtually all cases of both PAIS and CAIS. No gender change was observed. Molecular diagnosis was obtained in 96% of CAIS and in 87% of PAIS. There were 10 novel AR allelic variants (4 in CAIS - 2 small deletions, 1 missenseand 1 at splicing site and PAIS - 5 missenseand 2 synonymous variants (both causing a new exonic splicing site leading to a short AR protein). LH ranged from 9 to 48 UI/L (mean 19), testosterone from 190 to 1500 ng/dL (mean 438), without phenotype differences. Seminoma was identified in 2 out 24 (8%) individuals with CAIS (at 19 and 20 years of age). This rate was higher taking into account only those who underwent gonadectomy after puberty (16 years old or later: 2 out 17 (12%). Among PAIS there were 2 cases of NICG (at 3 and 19 years of age) and none of seminoma. Conclusion: Hormonal levels did not enable us to differ PAIS and CAIS. Inguinal hernia is a common clinical presentation of AIS. External genitalia appearance in PAIS influenced sex assignment. The psychosexual development in AIS usually complies with sex assignment. No gender change was observed. There is a risk of seminoma in CAIS, especially after puberty, which is not low enough to be ignored.
SUN-023 Changes in Microct Bone Density and Reduced Bone Formation in a “Postmenopausal” PCOS Rat Model
Authors: Comim Fabio Vasconcellos , Comim Fabio Vasconcellos , Mujica Lady Katerine S , Macari Soraia , Silva Tarcilia A , Barrioni Breno R , Stein Carolina S , Valente Fernanda , Miyazato Ligia G , Antoniazzi Alfredo Q , Moresco Rafael N , Premaor Melissa Orlandin
Published: May 2020

Polycystic ovary syndrome (PCOS) affects women during their entire lifespan. Evidence from the literature suggests an association of PCOS with decreased bone formation markers (osteocalcin and P1NP), although no conclusive data about the incidence of fractures exist. In the present study, we investigated the consequences of androgenization in rats on bone markers and femur microCT and the changes in these parameters after ovariectomy. This study was approved by the local Animal Ethics Committee. Briefly, Wistar rats (n= 38) were divided in 4 groups: 1) “Control OVX” (single dose of corn oil s.c. at day 5 of life and ovariectomy at day 100, n=9); 2) “Control SHAM” (n=9); 3) “Androgenized OVX”(single dose of testosterone propionate 1.25 mg s.c. at day 5 of life and ovariectomy at day 100, n=10); and 4) “Androgenized SHAM” (n=10). Full characterization of estrous cycles and weight was performed during growth, and all animals were euthanized at day 180 during metestrus/diestrous. Evaluation of glucose levels, lipids, estradiol, P1NP levels (a marker of bone formation), and analysis of the femur micro CT Skyscan 1174 (Aartselaar, Belgium) was performed in at least eight animals of each group. Ovariectomy increased the weight of Androgenized OVX rats on day 180: these animals were heavier than Control OVX, Control SHAM, or Androgenized SHAM (ANOVA p<0.001). However, metabolic changes were observed in ovary-intact Androgenized SHAM rats who exhibited higher total cholesterol (ANOVA p<0.001), increased LDL (ANOVA p=0.03), and elevated TyG index, a marker of insulin resistance (ANOVA p<0.001) against all other three groups. This group (Androgenized SHAM rats)also exhibited an increase in MicroCt bone density (g/cm-3) (mean + SEM) of 1.117 + 0.06 against the other - Control SHAM 0.8433 + 0.03, Control OVX 0.5527 + 0.001, and Androgenized OVX 0.6284 + 0.02 (ANOVA p< 0.001). Although the values of bone density between Control OVX and Androgenized OVX groups were similar, gonadal removal produced a different pattern of bone density reduction between Control OVX and Androgenized OVX (Two-Way ANOVA p=0.001). Moreover, we found P1NP levels significantly decreased in the Androgenized OVX group (mean + SEM) of 58.57 + 4.41 ng/ml against 88.02 + 8.49 ng/ml in Control OVX versus (ANOVA p<0.0001) indicating lower bone formation. Our results suggest that bone and metabolic features of Androgenized rats are affected by ovariectomy with a negative impact on bone formation.
SAT-246 A Case of Cabergoline Induced Pituitary Apoplexy in a Patient with Prolactinoma
Authors: Ahuja Ashim
Published: May 2020

Objective

To report a case in which Cabergoline led to pituitary apoplexy (PA) in a young female patient with a macroprolactinoma.

Methods

A 28 y/o F presented with 10 months of irregular menses followed by 6 months of amenorrhea. She reported a dull supranasal headache, and nipple crusting without obvious galactorrhea. She denied visual changes, dizziness nausea or vomiting. Her Prolactin (PRL) was elevated at 194ng/mL, and she was started on Cabergoline 0.25mg twice per week and sent for a pituitary MRI.

Four weeks later, the patient presented to the emergency department with an acute worsening of headache after being found to have a pituitary hemorrhage on MRI. On PE there were no obvious neurologic deficits. Neurosurgery recommended no acute intervention and she was managed conservatively.

Results

Labs prior to Cabergoline: bHCG (-), PRL 194 ng/mL; LH 3.1 µIU/mL; FSH 4.9 µIU/mL; Estradiol <11 pg/mL; Cortisol 11.44 ug/dL; TSH 1.080 µIU/mL; Free T4 0.76 ng/dL. Labs after 1 month of Cabergoline treatment: PRL 84.3 ng/mL; FSH 2.2 µIU/mL; LH 2.8 µIU/mL; TSH 1.23 µIU/mL; FT4 0.82 ng/dL; Cortisol 15.43 ug/dL. MRI 1 month after Cabergoline was performed and showed a 1.4 x 1.4 x 1.5cm hemorrhagic mass of pituitary gland.

Discussion

PA is the acute hemorrhage or infarction of the pituitary gland, commonly presenting with sudden onset of severe headache, visual field impairment, vomiting or altered mental status. However, like our patient, 25% of patients may present with subclinical apoplexy.

Bromocriptine and Cabergoline are the two main treatments for prolactinoma. Both have been linked to PA, though the number of reports on Cabergoline is much less. There are now 10 cases of apoplexy reported with Cabergoline.

PA can be spontaneous or precipitated by angiography, surgery, head trauma, hypertension, thrombocytopenia, diabetes, radiotherapy, coagulopathies, and Dopamine Agonists (DA). Most cases occur in older patients (50–60’s) with comorbidities, and incidence in patients <35 is rare.

Moreover, PA is more common in males. Therefore, PA presenting in a young, healthy female suggests that Cabergoline may have been the precipitating factor.

Conclusion

It is important to be aware that Cabergoline can precipitate PA in patients being treated for a Prolactinoma. We recommend a thorough history, physical exam and baseline imaging before starting Cabergoline therapy. We also recommend emergent imaging if there is an acute change in symptoms.
SUN-717 SG-2 a Novel Multi-Target Directed Ligand (MTDL) for the Treatment of Neurodegenerative Diseases (NDDS)
Authors: Sestito Simona , Runfola Massimiliano , Bandini Lavinia , Santucci Filippo , Origlia Nicola , Rapposelli Simona , Chiellini Grazia
Published: May 2020

NDDs are progressive multifactorial disorders that impair memory, cognition, movements, and general functioning. This deterioration is mostly due to inflammation triggered by aberrant protein deposition, oxidative stress and modification in lipid pathways. Because of these multifactorial aspects, the development of multi-target directed ligand (MTDL) could represent a potential strategy for the treatment of NDDs.

Recently, the thyronamine-like analog SG-2, originally developed as a synthetic TAAR1 agonist, has revealed to efficiently reprogram lipid metabolism and to produce memory-enhancement in mice1. Long-term potentiation (LTP) is one of the basic mechanisms of memory. LTP is inhibited by beta-Amyloid oligomers (Aβ), and in the early stage of AD it is selectively impaired in the entorhinal cortex (EC).

In the present study, to further expand our knowledge on the potential of this novel analog to act as a neuroprotective agent, we investigated if administration of SG-2 has any effect on LTP in EC of a transgenic model of AD (hAPP-J20 mouse).

Extracellular in vitro recordings were performed in EC slices from 2 month-old APP-J20 mice: field potentials were evoked in layer II after stimulation of the same layer and LTP was elicited by high frequency stimulation (HFS), consisting of three trains of 100 pulses at 100Hz. SG-2 (1 or 5μM) was administered for 10 minutes, starting 5 minutes before the delivery of HFS.

LTP cannot be elicited by HFS in mhAPP slices perfused with artificial cerebrospinal fluid (ACSF) alone. When we tried to rescue LTP in mhAPP slices using SG2 at the lowest concentration (1µM), 10 min perfusion with SG2 was not effective. In contrast, a higher concentration of SG2 (5 μM), rescued LTP to a level that was significantly higher than that observed in mhAPP slices alone (n=6; p=0.046), as well as in mhAPP slices perfused with SG2 1 μM (n=5; p=0.043). Our results suggest that SG-2 plays a neuroprotective effect, rescuing Aβ-induced neuronal dysfunction and might open new perspective in the study of AD. Metabolic reprogramming and neuroprotective functions for the histone deacetylase SIRT6 are well known, and a reduction of SIRT6 expression has been observed in patients with AD. Exposure of human neuroblastoma (SH-SY5Y) cells to SG-2 (1 or 10 μM) resulted in significant (p=0.044) over-expression of SIRT6, and concomitant activation of AMPK leading to the inhibition of mTOR phosphorylation, further underlying potential for SG-2 as a multi-target neuroprotective ligand.

Reference: (1) Bellusci et al. Frontiers in Pharmacology 2017; 8: 905.
MON-636 The Relationship Between Glucose Control & Cognitive Function in People with Diabetes After a Lacunar Stroke
Authors: Cukierman-Yaffe Tali , McClure Leslie , Risoli Thomas , Bosch Jackie , Gerstein Hertzel C , Benavente Oscar
Published: May 2020

Background & Objective Both lacunar strokes and diabetes are risk factors for dementia and cognitive dysfunction. Thus, elucidating modifiable risk factors for cognitive dysfunction in people with type 2 diabetes who experienced a lacunar infarct has large public health implications. One such factor may be glycemic status, as measured by glycosylated hemoglobin (A1C). Thus, the aim of this study was to assess the relationship between A1C and cognitive function in people with diabetes after a lacunar stroke. Research Design & Methods The effect of baseline and follow-up A1C on the baseline and the change in Cognitive Assessment Screening Instrument (CASI) score over time among participants with a median of 2 cognitive assessments (range 1-5) was examined in of 942 individuals with diabetes and a lacunar stroke who participated in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial (ClinicalTrials.gov number, NCT00059306). Results Every 1 % higher baseline A1C was associated with a 0.06 lower standardized CASI z-score (95% CI -0.101, -0.018). Higher baseline A1C values were associated with lower CASI z-score over time (p for interaction=0.037). A 1% increase in A1C over time, corresponded with a CASI score decrease of 0.021 (95% CI -0.0043, -0.038) during follow-up. All these remained statistically significant after adjustment for age, sex, education, race, depression, hypertension, hyperlipidemia, BMI, CVD, OSA, diabetic retinopathy, nephropathy insulin use and White Matter Abnormalities. Conclusion This analysis of 942 individuals with diabetes after a lacunar stroke demonstrates a relationship between A1C and change in cognitive scores over time. Intervention studies are needed in order to delineate if better glucose control could slow the rate of cognitive decline in this high risk population.
SAT-624 Predictive Ability of Lipoprotein Insulin Resistance (LPIR) Score in South Asians: A Comparison of Surrogate Indices of Insulin Sensitivity/Resistance
Authors: Fosam Andin , Grewal Shivraj , Armiyaw Abdul-Latif , Sarcone Camila , Rabel Antoinette , Auh Sungyoung , Muniyappa Ranganath
Published: May 2020

South Asians (SA) are at higher risk for developing insulin resistance (IR) and type 2 diabetes. Consequently, identifying IR in this population is important. Lack of standardization and harmonization of insulin assays limit the clinical use of insulin-based surrogate indexes of insulin resistance. The lipoprotein insulin resistance (LPIR) score, a metabolomic marker, reflects the lipoprotein abnormalities observed in insulin-resistant states. The reliability of the LPIR score to predict IR in South Asians is currently unknown. In this study, we aimed to evaluate the predictive accuracy of LPIR compared to other fasting-based surrogate indices in SA.

In a cross-sectional study of 59 non-diabetic SA subjects (age 36 ± 8 years, BMI 26.5 ± 5.2 kg/m2), we used calibration model analysis to assess the ability of the LPIR score and other simple surrogate indices [homeostasis model assessment (HOMA-IR), quantitative insulin sensitivity check index (QUICKI) and Adipose tissue insulin sensitivity (Adipo-SI)] to predict insulin sensitivity derived from the reference frequently sampled intravenous glucose tolerance test (FSIVGTT) and Minimal Model analysis (SiMM). LPIR scores were calculated using six lipoprotein particle concentrations and sizes measured by nuclear magnetic resonance (NMR) spectroscopy. Further, quantitative predictive accuracy and index comparisons were determined by root mean squared error (RMSE) of prediction and leave-one-out cross-validation-type RMSE of prediction (CVPE). Receiver operating characteristic (ROC) curve analysis was performed to determine how well LPIR distinguished insulin resistant individuals, categorized as an SiMM < 3.

As determined by calibration model analysis, Adipo-SI, HOMA-IR, and QUICKI showed moderate correlations with for SiMM (Adipo-SI: r = 0.66; HOMA-IR: r = 0.60; QUICKI: r = 0.57, p = <0.0001). No significant differences were noted among CVPE or RMSE from any of the routinely used surrogate indices when compared with LPIR. The ROC area under the curve was 0.76 (95% CI 0.64–0.87) suggesting that LPIR performed well in identifying insulin resistant subjects. The optimal cut-off in IR individuals was LPIR >46 (sensitivity: 75.9 %, specificity: 70.0%). We conclude that NMR-derived LPIR may be an appropriate index to assess insulin resistance in South Asians.
MON-659 Course of Puberty and Growth Spurt in Boys with Type 1 Diabetes
Authors: Shpitzer Hana , Lazar Liora , Shalitin Shlomit , Phillip Moshe , Vries Liat de
Published: May 2020

Background: Data on the course of puberty and pubertal growth in boys with Type 1 diabetes (T1D) are sparse.

Objectives: To study the course of puberty, pubertal growth and final height in boys with T1D as well as possible factors affecting these.

Methods: In this retrospective longitudinal study, 68 boys diagnosed with T1D between 1996-2009 who were pre-pubertal at diagnosis and had completed puberty served as the cohort. Collected were data on anthropometric measurements, Tanner stage, and HbA1c levels from diagnosis to final height (F-Ht). F-Ht was compared to parental height and to the data of the national health survey

Results – In the study cohort final height-SDS was lower than that at diagnosis. It was similar to parental Ht-SDS as well as to that of the national health survey (p=0.126). F-Ht was inversely related to average HbA1c during puberty (R=-0.27, p=0.045). Boys who presented with diabetic ketoacidosis at diagnosis were shorter than those who did not throughout the entire follow-up. Age at onset of puberty was significantly related to the age of maternal menarche (R=0.44, p=0.01) and to HbA1c levels in the year preceding puberty onset (R=0.36, p=0.01). Total pubertal growth was inversely related to HbA1c levels in the year preceding onset of puberty (average R=-0.3, p=0.03)

Conclusions: Boys with T1D diagnosed before puberty achieve final height similar to that of their parents and that of the general population. Diabetic ketoacidosis at the diagnosis is associated with diminished F-Ht. Age of pubertal onset and F-Ht are affected by genetic factors as well as by glycemic control before and during puberty.

These results emphasize the importance of tight metabolic control in adolescents, to enable growth within the genetic target.
OR15-05 Gain in Near Adult Height Using the Combination of an LHRH Analogue and an Aromatase Inhibitor in Early Maturing Girls with Compromised Growth. The “Gail” Study ISRCTN11469487
Authors: Papadimitriou Dimitrios T , Dermitzaki Eleni , Papagianni Maria , Kleanthous Kleanthis , Mastorakos George
Published: May 2020

Background. Third generation aromatase inhibitors (AI), as monotherapy, have never been used to increase predicted adult height in girls. Our previously published GAIL study has shown that the combination of anastrozole to an LHRH analogue for 24 months is safe and effective in ameliorating PAH in girls with early puberty +1.21 SDS (+7.51 cm) compared to inhibition of puberty alone +0.31 SDS (+1.92 cm), p=0.001 (1).

Objective and Hypotheses. We assessed the final height of the girls who participated in the GAIL study compared to the predicted after 24 months of combined treatment and additionally the efficacy of anastrozole monotherapy after completion of the combined treatment in further improving final height.

Methods. We measured adult (i.e. age 16.5 yrs) or near adult height (i.e. at bone age 14 yrs) of the 40 girls who participated in the GAIL study and were divided in two groups Group A (20 girls on anastrozole + leuprorelin) and Group B (20 girls on Leuprorelin alone). Group A was further randomized into two subgroups. Group A1 (10 girls), after completion of the combined therapy, received anastrozole 1 mg/day as monotherapy until bone age of 14 yrs with a 6-month follow-up. Group A2 (10 girls) had stopped the combined therapy at 24 months or 11 yrs of age and were recalled for adult (or near) height evaluation.

Results. Adult or near adult height (NAH) exceeded the predicted at the completion of the initial phase of the GAIL study in all three groups but the result was statistically significant only in Group A1: NAH-PAH = Group A1: +3.85 cm (+0,62 SDS) p=0.001, Group A2: +1,6 cm (+0,26 SDS) p=0.26, Group B: +1,7 cm (+0,3 SDS) p = 0.09. Gain in Group A1 was significantly greater to that of Group A2 (p=0.046) and Group B (p=0.035).

Conclusion. In early maturing girls with compromised growth, treatment for 2 yrs or until the age of 11 yrs with LHRH analogue plus anastrozole 1mg/day, the gain is +9.7cm in total when treated with anastrozole monotherapy until they reach NAH, whereas it is +7.4 cm if they do not continue with the monotherapy and only +3.6 cm when treated with an LHRHa only. As a result, the combination therapy continued with anastrozole monotherapy, ends in the shortest distance from target height. This implies that the addition of the anastrozole to an LHRHa apart from being safe, is effective in ameliorating substantially Near Adult Height making the intervention meaningful.

Reference:

(1) Papadimitriou DT, Dermitzaki E, Papagianni M, Papaioannou G, Papaevangelou V, Papadimitriou A. Anastrozole plus leuprorelin in early maturing girls with compromised growth: the “GAIL” study. Endocrinol Invest. 2016 Apr;39(4):439-46]
MON-193 Glucocorticoid Excess and Its Association with Metabolic and Cardiovascular Complications in Primary Aldosteronism
Authors: zhu Ke ying , chen huan , mengsi Liu , Feng Wen-huan huan , zhu da long , li ping
Published: May 2020

Objective: To investigate autonomous cortisol secretion in patients with primary aldosteronism and its effect on metabolism and cardiovascular events (CVE) in patients with primary aldosteronism (PA).

Methods: This study included 163 patients with PA and 105 sex- and age-matched patients with essential hypertension (EH). Clinical and laboratory data were collected. The expression of cortisol synthase (CYP11B1) and aldosterone synthase (CYP11B2) was investigated in adenoma tissues from 44 patients with aldosterone-producing adenoma (APA) by employing immunohistochemistry.

Results: 1) CYP11B2 was expressed in 36 patients with APA and was absent in 8 patients, while CYP11B1 immunoreactivity was detected in all tested patients with APA; 2) Compared with patients with EH, midnight cortisol concentration (104.81±90.86 vs 76.87±65.86), 24-h urine free cortisol level (726.04±309.87 vs 630.65±168.2), and cortisol level after 1mg-DST [35.6(27.6,75.73)vs 27.6(27.60,29.27)]were all significantly increased in patients with PA(all P<0.01); 3) Midnight cortisol concentration is positively associated with systolic blood pressure (SBP) (r=0.147 P<0.05), LDL-C (r=0.194 P<0.05), HOMA-IR (r=0.262 P<0.05), HOMA-β (r=0.313 P<0.05) and fasting insulin level (r=0.329 P<0.05) in patients with PA. In multiple linear regression analysis, midnight cortisol concentration was a postitive predictor for SBP (β=0.185 P<0.05), HOMA-IR (β=0.331 P<0.05) and HOMA-β (β=0.390 P<0.05); 4) Of the 163 patients with PA, 35 had a history of CVE, including 22 with stroke, eight with myocardial infarction, three with atrial fibrillation, and two with heart failure. The multivariate logistic-regression analyses revealed older age (OR 1.160 95%CI 1.041-1.294 P <0.001) and higher serum aldosterone level (OR 1.013 95%CI 1.000-1.026 P <0.05) were independent risk factors of CVE, serum cortisol level was not associated with the increased risk of CVE in patients with PA (OR 0.997 95%CI 0.985-1.009 P =0.570).

Conclusion: Excess cortisol secretion was common in PA. Cortisol excretion is correlated with metabolic disorders, but not associated with increased risk of CVE in patients with PA.
SAT-156 Shorter Hospital Stays Are Not Associated with Increased Readmission or Complication Rates in Patients Undergoing Laparoscopic Adrenalectomies
Authors: Sharma Rahul K , Huang Bernice , Lee James A , Kuo Jennifer H
Published: May 2020

Background : Traditionally, elective adrenalectomies have been performed as an inpatient procedure. However, the adoption of laparoscopic adrenalectomy as the gold standard has allowed for shorter postoperative stays. Our objective was to assess the safety of same-day discharge for patients undergoing laparoscopic adrenalectomy.

Methods : A retrospective cohort study of patients who underwent laparoscopic adrenalectomy from 2011-2017 was conducted using The American College of Surgeons National Surgical Quality Improvement Project (ACS NSQIP) database. Demographic data was obtained. Multivariable logistic regression models to assess the association between length of stay and both postoperative complication rates and 30-day readmission rates were regressed on age, sex, race, comorbidities, functional status, postoperative diagnosis, and operative time. Statistical significance was defined as p<.05.

Results : 5,611 unique patients who underwent a laparoscopic adrenalectomy were identified. 1,564 patients had a postoperative diagnosis of a pheochromocytoma (27.9%), 162 with Cushing’s syndrome (2.9%) and 210 (3.7%) had metastatic disease to the adrenal glands. The average postoperative length of stay was 2.4 days (SD=3.9). 93 patients (1.7%) were discharged on the same day as their surgery (POD0). 2,509 (44.7%) were discharged on postoperative day 1 (POD1), 1,558 (27.8%) on postoperative day 2 (POD2), and 1,451 (25.9%) after POD2. Longer hospital stays were predicted by male sex, non-white race, longer operating time, and postoperative complications in regression models.

351 patients (6.26%) experienced a complication postoperatively. Complication rates were 3.23% for patients discharged on POD0, 1.67% for those discharged on POD1, 3.27% for those discharged on POD2, and 17.57% for those discharged after POD2 (p<.01). An increased risk of postoperative complications was also associated with male sex, impaired functional status and the presence of multiple comorbidities in regression models.

290 patients (5.17%) experienced a readmission. Readmission rates were 4.30% for patients discharged on POD0, 3.67% for those discharged on POD1, 4.49% for those discharged on POD2, and 8.55% for those discharged after POD2 (p<.01). Multiple comorbidities, African American race, and post-operative complications were associated with higher readmission rates. Length of hospital stay was not associated with readmission rates in regression models.

Conclusions : Readmission rates were not significantly different for patients discharged on POD0 than POD1 after a laparoscopic adrenalectomy. Readmission rates were higher for patients who had complications or multiple comorbidities. Therefore, low-risk patients with uncomplicated laparoscopic adrenalectomies can be considered for same day discharge to potentially reduce hospital spending and resource utilization.
SAT-020 Fluoxetine Administration Influences Serotonin-Driven Bone Remodeling During Lactation and Pregnancy Outcome in Mice
Authors: Fricke Hannah P , Sheftel Celeste M , Hernandez Laura L
Published: May 2020

Selective serotonin reuptake inhibitors (SSRI) are the most commonly prescribed class of antidepressants during pregnancy and lactation. SSRI decrease bone mineral density (BMD) across all ages and sexes. Lactation is also characterized by increased bone resorption to mobilize calcium due to the demands of lactation and achieves this via a serotonin-induced hormonal cascade. This serotonin-mediated bone loss is normally restored after weaning but is persistent when an SSRI is administered during the peripartum period. We hypothesize that the long-term BMD loss associated with fluoxetine administration during lactation will be seen in two sequential lactations and will have a more dramatic effect on maternal bone loss after the second lactation at both weaning and 3 months post-weaning. Female C57BL/6 mice were randomized to receive the SSRI fluoxetine hydrochloride (20 mg/kg) or saline daily from the beginning of pregnancy (E0), determined by the presence of a vaginal mucous plug, through the end of lactation (D21). They were then given a 3-week rest period before undergoing a second lactation with the same study design. Each group is paired to an age-matched virgin cohort to provide a non-lactating control. This created the following treatments: saline dam (S), fluoxetine dam (F), saline virgin pair (SV), and fluoxetine virgin pair (FV). Dual-energy X-ray absorptiometry (DEXA) was used to measure BMD of all groups throughout the peripartum period. At the end of gestation (E17.5), BMD was decreased in both the F and FV groups, and the BMD of the FV group remained persistently lower than the SV group across all timepoints. Both the F and S groups exhibited a dramatic decrease in BMD between E17.5 and the beginning of lactation (D2), then a slight increase between mid-lactation (D10) and at weaning (D21). There was an overall interaction between treatment and time for all groups across the peripartum period (p<0.0001). During the first peripartum period, the F dams that were mated had significantly increased pregnancy loss (p=0.0041) and pup mortality post-parturition compared to S mice. Of the dams that were inseminated, determined by the presence of a mucus plug, 63% of successfully mated S dams (n=19) resulted in a full-term pregnancy. Of those S dams (n=12), 25% lost their entire litter at the beginning of lactation, and 75% maintained their litter until weaning. In the F dams that were successfully mated (n=37), only 35% resulted in a full-term pregnancy. We conclude that fluoxetine administration during the peripartum period decreases long-term maternal BMD and that fluoxetine exhibits a drug-specific effect on the dam resulting in a notably decreased incidence of a successful pregnancy.
SUN-937 A Case of Two Pathologies: Primary Hyperaldosteronism with a History of Pheochromocytoma
Authors: Akamnonu Chukwuka , Parikh Sahil , Wondisford Fredric Edward
Published: May 2020

Background: In patients with system based diseases, multiple pathologies coexisting in the same organ can go undiagnosed. We present a case of a patient with long standing hypertension recently diagnosed with Primary hyperaldosteronism in the setting of known Pheochromocytoma. Case: A 43 year old male with a history of Von Hippel Lindau (VHL), Pheochromocytoma status post right subtotal adrenalectomy 18 years ago, renal cell carcinoma, prediabetes, bilateral renal cysts, and hypertension presented to the clinic for evaluation of suspected hyperaldosteronism. The patient had a history of medication refractory hypertension associated with hypokalemia requiring potassium supplementation. The patient’s VHL disease involved the pancreas, adrenal, brain and spine which required surgery to remove tumors in these areas. His Pheochromocytoma resolved status post subtotal adrenalectomy. Recent imaging and laboratory work up showed a stable left adrenal nodule (unchanged over the years), unremarkable right adrenal status post subtotal adrenalectomy with normal serum and urine metanephrines. In September 2019 he was seen by his Cardiologist for persistent Atrial Fibrillation and subsequent workup for suspected hyperaldosteronism showed a morning plasma aldosterone of 44.4ng/dL (normal range 4–21 ng/dL), plasma renin activity of <0.6 ng/ml/hr (normal range 0.6–4.3 ng/mL), 24 hour urine aldosterone of 21mcg/24hr (normal range 3–20 mcg/24hr), Urine sodium excretion of 236 mmol/24hr (normal range 40-217mmol/24hr), and potassium of 3.5mmol/L (normal range 3.6–5.0 mmol/L). The diagnosis of Primary hyperaldosteronism was confirmed and the patient was subsequently scheduled for adrenal venous sampling. Conclusion: This case demonstrates how multiple adrenal pathologies can present in the same individual. There is paucity of data in the literature as to the existence of both Pheochromocytoma and primary hyperaldosteronism in the same individual or the pathophysiological connection between them. When the diagnosis of a disease affecting a specific organ has already been made, the discovery of a secondary pathologic process affecting such organ may end up getting delayed. Clinicians should be aware of this possibility.
SAT-254 Desmopressin Stimulation Test in a Pregnant Patient with Cushing’s Syndrome
Authors: Warachit Wasita , Porntharukchareon Thachanun , Sunthornyothin Sarat
Published: May 2020

Background: Cushing’s syndrome (CS) in pregnancy is a rare condition. Accurate diagnosis and appropriate treatment are necessary due to increased morbidity and mortality in the fetus and mother with active CS. However, hormonal changes during pregnancy and limitations in terms of teratogenicity complicates the diagnosis of CS. Clinical case: A 27-year-old female presented at gestational age (GA) of 8 weeks with a 2-month history of proximal muscle weakness. She had 20-kg weight gain in 2 years before hypertension, prediabetes and pulmonary tuberculosis developed at the age of 25. On physical examination, her blood pressure was 160/100 mmHg. She had moon face, buffalo hump, wide purplish striae and hirsutism without signs of virilization. At GA 9 weeks, her morning cortisol was 32 μ;g/dL (883 nmol/L). Her salivary cortisol was 0.7 μ;g/dL (19 nmol/L) and a mean 24-hour urinary free cortisol was 237 μ;g/d (654 nmol/d), which were above reference ranges. Adrenocorticotropic hormone (ACTH) were 48 pg/mL (11 pmol/L) and 40 pg/mL (9 pmol/L). Dehydroepiandrosterone sulphate was 378 μ;g/dL (10 nmol/L). A non-gadolinium enhanced magnetic resonance imaging (MRI) at GA 12 weeks did not reveal a pituitary mass. Desmopressin stimulation test was carried out at GA 14 weeks. Her baseline cortisol was 31 μ;g/dL (855 nmol/L) and ACTH was 35 pg/mL (8 pmol/L). Her ACTH increased 70% at 15 minutes after desmopressin stimulation, with an absolute difference between basal and peak ACTH of 24 pg/mL (5 pmol/L). MRI pituitary gland with gadolinium at GA 14 weeks revealed an 8-mm adenoma at right inferolateral aspect of pituitary gland. Transsphenoidal surgery with selective adenomectomy was done at GA 18 weeks without immediate complications. Pathological findings showed a segment of pituitary adenoma with ACTH positive cells. After surgery, her morning cortisol was 6 μ;g/dL (166 nmol/L). Hydrocortisone supplement was given and had been continued throughout pregnancy. She successfully gave birth to a term 2300-gram male infant. One year after delivery, she had spontaneous pregnancy and also delivered a term 3300-gram male infant. Cushing’s syndrome had been in remission for 2 years of follow-up. Conclusion: Hormonal changes during pregnancy lead to an increased in ACTH after 7 weeks of gestation. Desmopressin test can be a safe and reliable test to differentiate between ACTH-dependent and ACTH-independent CS. Because a non-gadolinium enhanced MRI may not always detect pituitary microadenoma, this raises the necessity of the use of MRI with gadolinium as an initial imaging in pregnant patients with ACTH-dependent CS. References: Brue T, Amodru V, Castinetti F. Management of Cushing’s syndrome during pregnancy: solved and unsolved questions. Eur J Endocrinol. 2018;178(6):R259-266.
MON-514 Detection of RAS Mutations and RET/PTC Fusions in Thyroid Cancer Using Microfluidic Digital PCR
Authors: Ylli Dorina , Patel Aneeta , Mendoca-Torres Maria Cecilia , Costello John , Bikas Athanasios , Wartofsky Leonard , Burman Kenneth D , Jensen Kirk , Vasko Vasyl V
Published: May 2020

Background:

The identification of somatic mutations and gene fusions is crucial for guiding therapeutic decisions in patients with thyroid cancer. Microfluidic digital PCR is currently considered as a technique of choice for highly sensitive detection of gene mutations/fusion. We recently demonstrated that dPCR is a useful tool for detection of BRAFV600E and TERT promoter mutations in thyroid tumors.

Objectives:

This study aimed to determine the analytic and clinical validity of dPCR for detection of RAS mutations and RET/PTC fusions in thyroid cancer tissue.

Material and Methods:

Thyroid tissues from 75 patients with PTCs (58 classical PTC (CPTC) and 17 follicular variant (FVPTC) were used for DNA and RNA extraction. The rare mutation SNP genotyping assays which were multiplexed for detection of mutant and wild type NRASQ61; as well as RET/PTC1 and RET/PTC3 were synthesized by Thermo Fisher Scientific. Digital PCR was performed using a QuantStudio 3D Digital PCR platform. QuantStudio Software was used for relative and quantitative data analysis.

Results:

NRASQ61 was detected in 0/58 CPTC and in 6/17 (35%) FVPTC. The ratios of mutant/total varying from 11.7% to 61.5%. Among patients with FVPTC there were no significant associations between the presence of NRASQ61 and patient’s age, sex, multifocal growth, extra-thyroidal invasion and lymph node metastases. The ratios mutant/total correlated with tumor size in patients harboring NRASQ61. In 23 cases, RET/PTC1 and RET/PTC3 transcripts were examined. RET/PTC1 and RET/PTC3 transcripts were detected in 3 and 1 case, respectively. RET/PTCs were detected in CPTC, but not in FVPTC. RET/PTC positive tumors were characterized by multi-focal patterns of growth, presence of extra-thyroidal invasion, and presence of lymph node metastases (4 of 4 cases with RET/PTC). There were not RET/PTCs positive tumors harboring simultaneously anomalies in RAS oncogene.

Conclusions:

Microfluidic digital PCR allows specific, sensitive and rapid detection of RAS mutations and RET/PTC fusions in thyroid tissue samples. Implementation of dPCR-based assays may facilitate analysis of thyroid tumors and support research in patients with thyroid cancer.
SUN-540 Inflammasome Components After Bariatric Surgery: Novel Targets for a Chronic Disease
Authors: Herrera-Martinez Aura D , Aguayo Vicente Herrero , Sez Prudencio , López-Cánovas Juan L , L-López Fernando , Gahete Manuel David , Molina Puerta María J , Continente Alfonso Calañas , Membrives Antonio , Jiménez Concepción Muñoz , Rebollo-Román Ángel , Alcántara Laguna María D , Castano Justo Pastor , Gálvez-Moreno María A , Luque Raúl M
Published: May 2020

Background: Obesity is a metabolic chronic disease with important associated morbidity and mortality. Bariatric surgery (BS) is the most effective treatment for keeping long-term weight loss in severe obesity and consequently decreases obesity-related complications including inflammation. Aim: to explore changes in the inflammasome components after BS and their relations with clinical and biochemical parameters at baseline and six months after surgery. Patients and methods: 22 patients that underwent BS (sleeve gastrectomy and roux-en-Y gastric bypass) were included. Epidemiological, clinical, anthropometric and biochemical evaluation was performed. Four groups of inflammasome components and inflammatory associated factors were evaluated: NOD-like receptors; inflammasome activation components; cytoquines and inflammation/apoptosis related components; and cell-cycle and DNA-damage regulators. Clinical-molecular correlations and associations were for the first time performed in a cohort of patients with morbid obesity that underwent BS. Results: The four groups of inflammasome components were dysregulated after BS. The mRNA expression of several factors was markedly decreased after BS, specially CXCL3, CCL8, TLR4, NLRC4 and NLRP12. Most changes were independent of the performed surgical technique. Inflammasome components displayed several clinical and biochemical correlations including the presence of baseline metabolic comorbidities (type2 diabetes, dyslipidemia and hypetension) and the body composition. Conclusion: the regulation of several inflammasome system components may explain the improvement and reversion of some obesity-related comorbidities after BS.