bluuebunny/crossref_metadata_2025 huggingface dataset:
MON-326 Non Functioning Pituitary Adenomas (NFPA): Sex Related Differences in Presentation, Clinical Features and Outcomes
Authors: Rosmino Josefina , Tkatch Julieta , Guitelman Mirtha Adriana
Published: May 2020

INTRODUCTION: NFPA are characterized as tumors without a typical hormonal hypersecretion syndrome. They are frequently diagnosed in the sixth decade, by visual field defects, hypopituitarism or incidentally. PATIENTS AND METHODS: retrospective and observational study that included 103 patients with NFPA (60 females) who were seen between 1999 and 2019 in our hospital. We compared and analyzed patients characteristics by sex: reason for consultation, hormonal status at diagnosis, invasiveness of the tumor through MRI, treatments and outcomeRESULTS: out of 103 patients, 58,2% were women (W). Men (M) were significantly older than women (56 vs. 45 yold. p=0,002). The presence of a macroadenoma was similar in both sexes (93%W vs. 94,7% M), however tumor invasiveness was more frequent in men (50% vs. 24,6%). Most men consulted for incidental finding (47,4% vs. 29,8%); most women consulted for symptoms related to the tumor(70% vs 52%): hypogonadism 31,6% W, 13% M; galactorrhea 17% W; visual field defects 21,7% W, 23,7%M, pituitary apoplexy 11,6% M. At baseline hormonal assessment hyperprolactinemia was more frequent (50,9% vs 42%) and higher in women (mean PRL levels 75 ng/ml vs. 37 ng/ml). Hypogonadism was more frequent in men (54% vs 42%) as well as hypopituitarism (15% vs. 10,5%). Surgery was the most used therapy in both sexes (69% M vs. 73%W) but males required more frequently second surgery and radiotherapy than females (15% vs. 5% and 10% vs. 5% respectively). Gonadotropin secreting adenoma was diagnosed in 62% of men and 37,5% by tumor immunohistochemistry, in the 45% of women who presented negative immunostaining the presence of a gonadotrophic lineage is not ruled out, median Ki-67 labeling was low in both sexes (2%). After surgery 66% of men and 37% of women showed tumor remnant > 1cm (p=0,001), tumor regrowth was seen in 38,4% men and 10,4% women (p=0,03). Hypogonadism was greater in men than in women (56% vs 39%). Ninety two percent of men and 60,9% of women developed some degree of pituitary deficiency after surgery (P<0,001). Men showed a higher degree of complete hypopituitarism compared to women (pretreatment 15% vs 10,5%, post treatment 32% vs 13%). CONCLUSION: NFPA in men are usually diagnosed incidentally at an older age, are more invasive at presentation with a higher incidence of pituitary dysfunction. Moreover, they presented with greater rate of tumor regrowth and hypopituitarism after surgery. NFPA in women are diagnosed earlier due to endocrine symptoms, had lower degree of invasiveness with better outcomes after treatment. Sex related differences in NFPA may be associated with the delay in diagnosis, although a more aggressive biology cannot be discarded.
SAT-080 SLC29A3 Pathogenic Variant as a Causal for Dysosteosclerosis, a Poor Osteoclast Form of Osteopetrosis
Authors: Seiltgens Cristian , Rauch Frank , Bardai Ghalib
Published: May 2020

Background: Dysosteosclerosis (DSS) is a rare autosomal recessive form of osteopetrosis characterized by metaphyseal osteosclerosis and platyspondyly. At the histopathological level, a paucity of osteoclasts has been described when the disease presents genetic heterogeneity. SLC29A3 encodes a nucleoside transporter, that colocalizes intracellularly on the lysosomal membrane, is essential for lysosomal function and which is expressed in osteoclasts. Clinical case: We present a female patient from a nonconsanguineous camerunense family with DSS. Her first fracture at the age of 1 year occurred in the proximal right humerus following a very mild trauma. Subsequently she was referred to our clinic at the age of 1.8 months. At the last evaluation in our clinic at the age of 5.6 years she had suffered 5 femur fractures, 2 humerus fractures and a tibia/fibula fracture. XRays shown cortical thickening and widening of the diaphysis of the long bones, cranial base sclerosis, broad ribs with sclerosis and platyspondyly. Bone marrow biopsies and bone biopsy were not performed. The subject did not have any neurological symptoms, dental anomalies or present any dermatological issues. Dual-energy X-ray absorptiometry of the individual showed a lumbar spine BMD Z-score of +8 at 20 months of age, +7.1 at 3 years 5 months, +6.4 at 4 years 6 months and +5.1 at 5 years 6 months of age. TRACP 5 B 4.7 U/L is low in concordance with an osteoclast poor osteopetrosis, and the RANKL>>2.1 ipMol/L is high. On the other hand, CTX 1.298 ng/mL is normal. We identified and confirmed the homozygous pathogenic variant p.Arg386Gln in SLC29A3 using whole exome sequencing and sanger capillary electrophoresis.Conclusion: In summary, we show that a homozygous change in exon 6 of SCL29A3 (NM_00074; c.1157G>A; pArg386Gln) results in a phenotype of Dysosteosclerosis, adding a case to the small group of patients were pathogenic variants in this gene have been described causing sclerosing bone dysplasias with hallmarks of dysosteosclerosis. Interestingly, the other DSS cases and H syndrome cases confirms the clinical heterogeneity of disorders caused by mutations in SLC29A3 and the lack of a clear genotype-phenotype correlation. Phenotypically is also interesting to show that in our patient the bone mineral density has been decreasing over the time, with the concording increasing of TRAB5b. More mutations and functional investigations are needed to get a clearer picture for SCLC29A3 and how is involve in the process of osteoclast differentiation and activity.
SAT-036 Redefining Eunuchoid Body Proportions in Adults
Authors: Singh Santosh Kumar
Published: May 2020

Different population groups have different normal adult body proportions.A retrospective study was done on 100 males with age range of 20 to 58 years.Thirty (30%)males had arm span greater than height and upper segment and lower segment ratio(US/LS) below 0.9 which was a proposed criterion for eunuchoid body proportion by Winters.1Moreover,sixty-three(63%) males had arm span greater than 5 cm which was greater than the 2 cm criterion of Santen.2 Only three(3%) males had arm span 1 SD above mean(172.55 ± 12.01 cm) and US/LS 1 SD below mean(0.91 ± 0.04 cm). Hence,eunuchoid body proportions in adults should be defined in terms of SD from mean for the particular sex and race.The body proportion could be due to delayed puberty in Indians compared to the Western population.

References

1.Winters SJ:Clinical Disorders of the Testis.In Leslie J Degroot eds.Endocrinology.3rded. W. B. Saunders Company 1995;2377-2403.

2.Santen RJ:The Testis.In P.Felig et.al. eds.Endocrinology and Metabolism.2nd ed.McGraw Hill,1981,821-905.
MON-001 Peripartum Sertraline (Zoloft®) Increases Pup Mortality Immediately Postpartum
Authors: Sheftel Celeste , Sartori Luma C , Manuel Robbie , Fricke Hannah , Bell Autumn , Mulvenna Elizabeth , Hernandez Laura L
Published: May 2020

Peripartum and postpartum depression can be detrimental to both the mother and the developing child. Use of antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), is common during the peripartal period and SSRIs have been the leading prescribed antidepressant to treat maternal depression. One of the most commonly prescribed SSRIs is sertraline (Zoloft®) because of the limited fetal teratogenic effects observed, unlike maternal paroxetine (Paxil®) usage which can manifest in fetal cardiovascular defects. Fluoxetine (Prozac®), like sertraline, has previously been shown to have limited teratogenic effects, however, we have shown treatment with fluoxetine for the entire period of pregnancy and lactation in mice compromises pup bones at weaning resulting in decreased long bone length and head circumference. Furthermore, maternal fluoxetine usage results in a sustained reduction in maternal bone mineral density post weaning, which may lead to long-term osteopenia, putting the mother at risk for bone-related disorders later in life. We hypothesized sertraline, like fluoxetine, will compromise maternal bone postpartum and fetal bone development at weaning. Treatment with sertraline in C57BL/6 dams throughout pregnancy and lactation reduced litter size (5.4 pups/dam) and increased pup mortality during the first 24 hours postpartum (20% dead pups/litter) compared to controls (6.8 pups/dam, 5% dead pups/litter, respectively; P < 0.018). Maternal calcium transporters (Orai1 and Serca2) were downregulated in the mammary gland in sertraline-treated dams on day 21 of lactation (P < 0.0032). Together, our data suggests in utero pharmacological exposure to sertraline may induce a failure to thrive in the pups and alters calcium metabolism in the dam. SSRI exposure during pregnancy and lactation may adversely affect the developing neonate(s) as well as have lasting impacts on the mother.
SUN-235 Deficient Fear Extinction in PRKAR1A-Defective Mice
Authors: Keil Margaret , Paradiso Enrica , Keil Rita S , Ugolini Maddalena , Harris Evan , Wu T John , Stratakis Constantine A
Published: May 2020

Background: The role of the cAMP/PKA signaling in molecular pathways involved in fear memory is well established: PKA is required for fear memory formation and is a constraint for fear extinction. Previously we reported that a Prkar1a heterozygote (HZ) mouse that was developed in our lab to investigate Carney complex (CNC), the disease caused by PRKAR1A mutations, showed brain region-specific increased PKA activity that was associated with anxiety-like behavioral phenotype and threat bias (Keil, 2010, 2013). We hypothesized that Prkar1a+/- (HZ) mice would have deficits in fear extinction behavior. Brain derived neurotrophic factor (BDNF) has a critical role in formation of fear memory and its transcription is regulated by PKA/CREB. A mouse model with down regulation of PKA provides an opportunity for the first time to investigate the effect of altered PKA signaling on fear conditioning and extinction.

Method: Fear conditioning, fear extinction learning, and fear extinction recall were tested in adult male HZ and wild-type (WT) mice as follows: fear conditioning training followed 24hr later by extinction training (new context), then 24hr later by extinction recall training. Percentage of time freezing was used to assess conditioned fear response. We measured BDNF gene expression in brain regions after completion of extinction recall training.

Results: As expected, fear conditioning (learning) behavior was similar in HZ and WT mice. However, HZ mice showed a significant deficit in the early phase of fear extinction learning compared to WT. There was no difference in extinction recall between genotypes. Alterations in BDNF gene expression in the prefrontal cortex and amygdala was associated with deficit in fear extinction.

Conclusion: Mice with a downregulation of Prkar1a gene demonstrate intact fear conditioning but impaired fear extinction learning, consistent with prior studies that report that PKA inhibition is necessary to facilitate extinction learning. Prkar1a+/- mice provide a valuable model to investigate impaired fear extinction to identify mechanisms for therapeutic targets for anxiety and trauma-related disorders.
OR06-05 Inadequate High Mitochondrial ATP-Synthesis Explains “Non-Fatty-Liver” in Patients with Acromegaly
Authors: Fellinger Paul , Wolf Peter , Pfleger Lorenz , Martin Krssak , Kristaps Klavins , Stefan Wolfsberger , Alexander Micko , Patricia Carey , Bettina Gürtl , Vila Greisa , Raber Wolfgang , Clemens Fürnsinn , Scherer Thomas , Siegfried Trattnig , Kautzky-Willer Alexandra , Krebs Michael , Yvonne Winhofer
Published: May 2020

Background

Patients with active acromegaly exhibit low hepatocellular lipid content (HCL) despite pronounced insulin resistance. This contrasts the strong association of insulin resistance with non-alcoholic fatty liver disease in the general population. Acromegaly may therefore help to elucidate antisteatotic pathways. Since low HCL in acromegaly might be caused by changes in oxidative substrate metabolism and interorgan crosstalk we investigated mitochondrial activity and plasma metabolomics as well as lipidomics in active acromegaly.

Approach & Results

Patients In this cross-sectional study, 15 patients with active acromegaly (ACRO) and 17 healthy controls (CON) matched for age, BMI, gender and body composition were included. All participants were invited to undergo 31P/1H-7T-MR-spectroscopy of the liver and skeletal muscle, as well as plasma metabolomic profiling and an oral glucose tolerance test.

In comparison to CON, ACRO were insulin resistant, and showed significant lower HCL but their hepatic ATP-synthesis rate adjusted to HCL was significantly increased (h_kATP:0.19[0.14;0.24]vs0.28[0.22;0.34]s-1);p=0.024). Furthermore, the HCL-adjusted ratio of unsaturated to saturated intracellular fatty acids was decreased in ACRO (8.4%vs25.5% of HCL,p<0.04). In skeletal muscle, intramyocellular lipids and ATP-synthesis rate were significantly decreased in ACRO. Plasma lipids and lipidomics did not differ between ACRO and CON, but decreased levels of carnitine species were observed in ACRO.

Conclusions

The dissociation of hepatic lipid content and peripheral insulin resistance in acromegaly is associated with high mitochondrial activity as indicated by liver specific upregulation of the ATP-synthesis rate. This is paralleled by a decreased ratio of unsaturated-to-saturated lipids in hepatocytes and by a change in circulating carnitine species, also reflecting an increased mitochondrial activity. Our findings hint at potential direct effects of growth hormone excess on hepatic lipid and energy metabolism.
MON-109 Modulator of Gut Barrier, Zonulin Was Associated with Waist to Height Ratio in Adolescents
Authors: Kim Ki Eun , Kim Ok-Hyang , Han Sol , Sheen Youn-Ho , Kim Soo-Yeon
Published: May 2020

Background: Zonulin is the endogenous protein known to control the permeability of intestinal tight junction reversibly. Zonulin is actively engaged in intestinal innate immunity and is over-expressed in autoimmune diseases where tight junction of intestine plays a pivotal role, such as celiac disease, malabsorption disorder, and type 1 diabetes. Waist-Height ratio was well known as one of indices of obesity and also Waist-Hip ratio was known of abdominal obesity. We investigated that the associations among Waist-Height, Waist-Height ratio, and the level of Zonulin by assessing obesity-related biomarkers, such as liver enzymes, lipid profiles, and insulin resistance, in a population of adolescents.

Methods: The study included 198 adolescents aged 12-18 years; 92 were overweight/obese and 106 were of normal-weight. We assessed anthropometric and laboratory measures, including body mass index (BMI), BMI z-score, Waist-Height, Waist-Hip ratio, blood pressure, liver enzyme levels, lipid profiles, and insulin sensitivity. Serum Zonulin levels were measured using an enzyme-linked immunosorbent assay.

Results: The mean age of the participants was 15.2±2.5 years. Circulating serum Zonulin levels were significantly increased in overweight/obese participants compared with those in normal-weight participants (P=0.042). Zonulin levels were significantly and positively associated with BMI, BMI z-score, alanine aminotransferase levels, triglyceride, fasting insulin, and insulin resistance as indicated by the homeostasis model assessment of insulin resistance (HOMA-IR) (all P<0.05). In multivariate linear regression analysis, alanine aminotransferase (P<0.0001), triglyceride (P<0.0001), and HOMA-IR (P=0.001) contributed independently to circulating Zonulin levels after controlling for the effect of BMI z-score. Zonulin levels were more strongly associated with Waist-Hip ratio rather than Waist-Height ratio.

Conclusions: Zonulin was associated with indices of obesity. Waist-Hip ratio was more strongly associated with levels of Zonulin. The positive correlation between these parameters suggests putative pathophysiological mechanism linking Zonulin to metabolic dysfunction in adolescents.
SAT-717 Region-Specific Effects of the Exposome on Brain Monoamine Levels in Female Rats
Authors: Kaimal Amrita , Hooversmith Jessica , Mansi Maryam H Al , Holmes Philip V , MohanKumar Sheba M J , MohanKumar Puliyur S
Published: May 2020

Prenatal programming with endocrine disrupting chemicals (EDCs), in particular the ubiquitous plasticizers bisphenol A (BPA) and di(2-ethylhexyl) phthalate (DEHP), can induce long-lasting behavioral changes in rats. Additionally, changes in estrogen are correlated with the development of mood disorders in women; however, the underlying neurobiological mechanisms are unclear. This study was conducted to determine the cumulative effects of prenatal exposure to EDCs followed by chronic estradiol treatment in adult female rats on monoamine levels in the prefrontal cortex (PFC) and hippocampus (HC). Dams were orally administered saline (control; 10 µL/kg), BPA (B; 5 µg/kg), DEHP (D; 7.5 mg/kg) or a combination of BPA+DEHP (B+D) during days 6 through 21 of pregnancy. Adult female offspring were sham-implanted or implanted with pellets that release 17β-estradiol (E2) for 90 days (20 ng/day; Innovative Research America). The offspring then underwent a battery of behavioral tests at the end of treatment. Brains collected from the offspring were sectioned and the PFC and HC were microdissected and analyzed for levels of norepinephrine (NE), dopamine (DA) and serotonin (5-HT), using High-Performance Liquid Chromatography (HPLC). Significant reductions in monoamine levels were observed in the PFC while NE and 5-HT levels were markedly reduced in the HC after prenatal exposure to D or BD. BPA’s effects on monoamines were comparatively modest. E2 exposure increased DA but decreased 5-HT levels in the PFC of control animals. Prenatal exposure to EDCs made the offspring non-responsive to E2. The marked reduction in monoamine levels could have implications for learning and memory.
OR13-01 Comparison of Vitamin D Metabolism in Deficient and Sufficient States
Authors: Zhukov Artem , Povaliaeva Alexandra , Pigarova Ekaterina , Dzeranova Larisa , Bogdanov Victor , Ioutsi Vitaliy , Rozhinskaya Liudmila
Published: May 2020

Objective: to study the differences in calcium-phosphorus and vitamin D metabolism in healthy individuals with deficient and sufficient baseline state of vitamin D. Materials and methods: The study included 16 young conditionally healthy individuals, divided into two equal groups: with levels of 25(OH)D below and above 30 ng/ml determined by the immunochemiluminescent method (Group A and Group B respectively; DEQAS certified). All participants were evaluated for the biochemical parameters of blood and urine, characterizing calcium-phosphorus metabolism, PTH by commercial methods, and vitamin D metabolites (25(OH)D3, 25(OH)D2, 3-epi-25(OH)D3 and 24,25(OH)2D3) by HPLC/MS-MS before oral intake of 150 000 IU of an aqueous solution of cholecalciferol and 7 days after administration. Results: At baseline, the level of vitamin D metabolite 25(OH)D2 in Group B was lower with no significant differences in other studied parameters. In group A, strong positive correlations were observed between levels 25(OH)D3 and 3-epi-25(OH)D3, 24,25(OH)2D3, while in group B there were no such associations. After taking a loading dose of cholecalciferol, the groups showed generally similar changes in the studied vitamin D metabolites: a statistically significant increase in 25(OH)D3, 3-epi-25(OH)D3, a decrease in 25(OH)D2, and a ratio of 24,25(OH)2D3 to 25(OH)D3. However, the level of 24,25(OH)2D3 did not change in group B, with a significant increase in group A. The medians of the studied biochemical parameters in blood/urine, as well as PTH, remained unchanged in both groups. Conclusion: In patients with inadequate baseline levels of 25(OH)D, after a loading dose of cholecalciferol, there is a tendency to formation of more inactive forms of vitamin D. These deviations in the metabolism of vitamin D need to be clarified, since they can potentially affect the effectiveness of cholecalciferol therapy.
SAT-244 Inflammatory Rathke Cleft Cyst Caused Hypothalamic Panhypopituitarism
Authors: Mariko Tangiku , Ishizuka Tatsuo , Fujioka Kei , Inui Saori , Tani Hideki , Maruyama Takako , Yamada Kouji
Published: May 2020

Background: Hypothalamic panhypopituitarism was a rare disease which was caused by brain tumors such as Rathke cyst, germinoma, malignant lymphoma and craniopharyngioma, and vascular accidents such as thrombosis and hemorrhage. We have found a rare case of hypothalamic panhypopituitarism occurred by the inflammation of Rathke cyst. Case presentation: A 77-year-old woman was admitted to our hospital because of severe headache, nausea, vomiting and fever. Hyponatremia (Na 131 meq/L) and increased CRP level (0.20 mg/dl) and no finding of gastroenterological examination and abdominal CT scanning were observed. Endocrinological examination revealed low levels of anterior pituitary hormones such as GH, LH, FSH and ACTH and increased PRL levels and low level of serum cortisol. Simultaneous CRH, TRH and LH-RH stimulations tests indicated low responses of TSH, LH, FSH and PRL and hyperesponse of ACTH (from 2.4 to 251 pg/ml). Radiological examination by enhanced MRI revealed high intensity of T2-weighted images and low and partial high intensities of T1-weighted images in swelling of pituitary gland and vanishment of high intensity of posterior lobe in T2-weighted images suggesting that the inflammatory wall of Rathke cyst. We searched previous data of ACTH and cortisol levels which showed normal level of ACTH (55.2 pg/ml) and cortisol 18.8 μ;g/dl) when headache and nausea arouse on 50 days before. Based on above results patient was diagnosed as hypothalamic hypopituitarism due to inflammatory Rathke cyst. Therefore, patient was treated with hormone replacement therapy by 20 mg of hydrocortisone. After these treatment, polyuria, urinary low osmotic pressure and hypernatremia appeared due to partial diabetes insipidus caused by the impairment of posterior lobe in pituitary gland, and diagnosed by the examination of vasopressin test. This patient was also treated by the oral desmopressin acetate hydrate (60 μ;g/day), and has been well-tolerated in the outpatient clinic. Conclusion: These results suggested that inflammatory Rathke cyst with inflammatory changes in hypothlamo-pituitary system raised a rare case of hypothalamic panhypopituitarism.Reference: Nishioka H. et al.: Clin Endocrinology (Oxf) 2006:64:184–188
SUN-196 Persistent Hyperkalemia After Unilateral Adrenalectomy for Aldosteronoma
Authors: Ammana Hima Reddy , Yuditskaya Susan
Published: May 2020

Introduction

Following unilateral adrenalectomy, some patients experience persistent hyperkalemia. This has been attributed to hypoaldosteronism due to severe suppression of aldosterone synthesis in the contralateral adrenal gland. Additionally, excess aldosterone leads to glomerular hyperfiltration masking kidney dysfunction, which can then manifest after cure with CKD-related hyperkalemia.

Case Presentation

We report a case of 51-year-old male who was diagnosed with hypertension in his late 30s. He required a beta-blocker and calcium channel blocker (CCB) for 10 years, and eventually developed hypertensive nephropathy. With worsening lower extremity edema, he was switched from a CCB to an angiotensin receptor blocker. Soon afterwards, he presented with hypertensive emergency and was discovered to have significant hypokalemia (K 2.1 mmol/L), prompting work up for primary aldosteronism.

Biochemical evaluation revealed an elevated aldosterone to renin ratio of 38 [(ng/dL)/(ng/mL/hr)] and adrenal protocol CT scan revealed a 1.9 cm left adrenal nodule with benign characteristics. Adrenal vein sampling showed marked lateralization of excess aldosterone to the left adrenal gland, with proper catheter placement demonstrated in each adrenal veins (5-fold cortisol gradient bilaterally). He was started on spironolactone and 6 weeks later, underwent an uncomplicated laparoscopic left adrenalectomy. Spironolactone was discontinued

Serum K level was normal at 4.8 mmol/L immediately postoperatively. Ten hours later, his K went up to 6.6 mmol/L which was confirmed by repeat blood work, accompanied by worsened renal function (Cr 2.5 mg/dL up from a of baseline 2.0). His hyperkalemia persisted in the 5.0 – 6.0 range despite IV Calcium Gluconate, Insulin and D50. Oral potassium binders were avoided due to concerns about ileus. Upon recognition of the possibility of hypoaldosteronism, we recommended a NaHCO3 gtt, with subsequent normalization of serum K. We avoided initiating fludrocortisone in the short term, due to uncertainty about duration of hypoaldosteronism, & because he was still requiring two antihypertensive agents. Plasma aldosterone 2 wks after surgery was fully suppressed, confirming suspicion of hypoaldosteronism. He has been managed successfully with oral sodium bicarbonate tablets, remaining normokalemic at 3 weeks post-surgery.

Conclusion:

Here we present a case of persistent hyperkalemia following resection of a signficantly biochemically active and long-standing aldosteronoma, which was successfully managed with sodium bicarbonate. We attribute the post-operative hyperkalemia in this patient to a combination of hypoaldosteronism due to deep suppression of the mineralocorticoid production of the contralateral adrenal, as well as unmasking of more severe kidney dysfunction than was he previously thought to have once aldosterone excess was withdrawn.
OR12-06 Nuclear Receptor CAR Protects Female Mice from the Development of Diet-Induced Nonalcoholic Fatty Liver Disease
Authors: Oliviero Fabiana Layla , Lukowicz Céline , Mary Lucile , Lakhal Laila
Published: May 2020

NAFLD (Non Alcoholic Fatty Liver Disease) has become the most common cause of chronic liver disease in many developed countries worldwide and represents a major health concern. The prevalence of NAFLD is sexually dimorphic with men suspected to be more susceptible to the development of hepatic steatosis than women. Women are mostly protected until hormonal imbalance induced by menopause. Nuclear receptor CAR (Constitutive Androstan Receptor) is at the crossroads between endocrine and metabolic regulations and could therefore represent an interesting therapeutic target. It is primarily expressed in the liver and involved in the catabolism of hormones such as thyroid hormones, corticosteroids and estrogens. In addition, several studies reveal a metabolic role of CAR through regulation of major hepatic pathways such as neoglucogenesis, beta-oxidation and de novo lipogenesis. Our research is aimed at better understanding the role of CAR using a mouse model genetically deficient for CAR. To explore the metabolic functions of CAR, knock-out male and female mice were subjected to a high fat diet (HFD) for 16 weeks. Concomitant CAR deletion and high fat diet induces sexually dimorphic metabolic disorders. Knock-out of CAR in males exacerbates HFD-induced fasted hyperglycemia whereas in females, it aggravates body weight gain and adipose tissue accumulation. In accordance with epidemiological studies revealing a protection of women from the development of hepatic steatosis, HFD-fed WT female mice present less important hepatic steatosis than HFD-fed WT male mice. However, following CAR deletion, HFD-fed female mice develop a severe steatosis along with important hepatic injury. Ongoing studies aim to understand the transcriptomic and endocrine dysregulations that may explain these phenotypes. These results reveal a previously unrecognized dimorphic role of CAR in energy homeostasis and highlights its involvement in the protection of female mice towards the development of hepatic steatosis. Overall, this research provides further insights in the pathogenesis of NAFLD and its dimorphic prevalence.
SAT-061 Severe Hypocalcemia in an Infant with Abnormal Microarray and Dysmorphic Features
Authors: Jo Inha , Mantis Stelios , Minutti Carla
Published: May 2020

Introduction:

In pediatrics, hypocalcemia is observed most often in an ICU setting. It can be associated with acute or chronic illnesses. We present a 1 month old male infant with abnormal microarray who presented to the PICU for seizures secondary to severe hypocalcemia.

Case presentation:

A 1 month old male was admitted to PICU with new onset seizures. Past history was remarkable for NICU hospitalization for respiratory distress, dysmorphic features with genetic evaluation revealing chromosome 10p15.3p14 deletion and chromosome 6p25.3p24.3 duplication with normal karyotype, muscular VSD, neonatal cholestasis, left hydronephrosis and congenital hypothyroidism. Labs obtained during NICU stay did not reveal hypocalcemia at the time. Basic lab work-up done at time of admission showed low Ca level of 5.6, elevated Phos of 9.3 and Mag level of 1.6. Thyroid work-up was within normal.

Pediatric endocrinology was consulted for hypocalcemia.

Further work-up showed Ca of 7.2, drawn after calcium gluconate riders and on calcium infusion rate at 5 mg/kg/hr, Mg of 1.8, Phos of 6.4, PTH of 36.2 and vitamin D-25 OH of 10, which was most consistent with hypoparathyroidism, likely due to his underlying genetic mutation, given inappropriately normal PTH. We recommended to continue Ca infusion as needed up to 80 mg/kg/day to maintain normal Ca levels and to provide 2000 units of vit D for 6-12 weeks and Calcitriol 0.25 mcg daily for 1 week with monitoring of levels.

Patient’s remainder of hospital course was complicated by need for intubation, arrhythmia unrelated to hypocalcemia, sepsis, acute tubular necrosis, which prolonged patient’s need for IV calcium and length of hospitalization. Patient’s electrolytes were normalized and he was able to transition to 25 mg/kg/day PO supplements and 1000 units of vit D with improved levels. He was discharged on these supplements with follow-up.

Conclusion:

This is a case of severe hypocalcemia secondary to primary hypoparathyroidism from underlying genetic mutation with chromosome 10p15.3p14 deletion. Patient’s complicated hospital course including sepsis and acute tubular necrosis had prolonged the need for calcium infusion until he was eventually transitioned to PO calcium supplementation. It is interesting that to note the association of his underlying genetic mutation and hypoparathyroidism as there has not been any specific pediatric case described with patient’s genetic mutation.

1.
SUN-520 Graves Disease and T3 Thyrotoxicosis: A Case Report
Authors: thalambedu Nishanth , iqbal Iqra , khanal Shristi , Khan Muhammad Atique Alam
Published: May 2020

Introduction: Hyperthyroidism is one of the common problems in the world of endocrinology. Identifying the type of thyrotoxicosis is crucial before starting treatment. We present a case of a 37-year-old woman presented with hyperthyroidism and was started on methimazole. Her symptoms persisted and further workup showed T3 thyrotoxicosis. Her symptoms improved after switching her to PTU. She eventually underwent thyroidectomy.

Case description: Thirty-seven-year old African American woman presented to her primary care physician(PCP) with symptoms suggestive of hyperthyroidism for three months. Her past medical history is significant for recent delivery one year ago. Her Physical exam is pertinent for hypertension of 160/80 with a heart rate of 120. Her neck is diffusely enlarged with bilateral bruits. Bilateral lid retraction with lid lag was noted along with left lid proptosis. There were no tremors or leg swelling noted. Her Initial workup showed sinus tachycardia in the electrocardiogram. Her TSH level was <0.010 and a free T4 level of 3.48. Ultrasound showed diffuse enlargement of the thyroid gland with no focal nodule. She was started on methimazole 10mg twice daily and metoprolol 25mg twice daily.

Three months later, she presented to the emergency room(ER) with tachycardia of 130 and hypertension of 170/85. Work up showed a TSH level of <0.010 and a free T4 level of 3.94. She was compliant with medications. When free T3 levels were checked it turned out to be >30. She was diagnosed with T3 Thyrotoxicosis and was started on propylthiouracil 150mg every 8 hours. Her metoprolol was increased to 50mg every 12 hours. Her symptoms improved and she finally underwent surgery for thyroidectomy.

Discussion: Hyperthyroidism is seen in about 1 in 5000 with a strong female predominance. Graves disease, the most common cause of hyperthyroidism is due to excess production of TSH receptor stimulating antibodies. Hyperthyroid patients with graves disease sometimes have a disproportionate increase in serum T3 levels when compared to serum T4. This is thought to be due to increased T3 production or extrathyroidal conversion of T4 to T3. It is very crucial to identify the free hormone levels in a new patient with hyperthyroidism because of the difference in management. Antithyroid drugs are traditionally the first-line treatment option along with beta-blockers prior to definitive therapy like radioactive iodine or thyroidectomy. The main drugs used are methimazole and propylthiouracil(PTU). Methimazole is more commonly used than PTU because of its rapid efficacy, longer duration of action and less adverse effects. For patients with T3 thyrotoxicosis, PTU is preferred as it is known to reduce the peripheral conversion of T4 to T3. Our patient medication was changed from methimazole to PTU, after which she started to notice improvement. She eventually underwent definitive treatment with thyroidectomy.
SUN-028 Concomitant Mutations in the POR and AR Genes in a Boy Presenting with Micropenis and Premature Adrenarche
Authors: Dermitzaki Eleni , Manolakos Emmanouil , Kleanthous Kleanthis , Mastorakos George , Papadimitriou Dimitrios T
Published: May 2020

Background: Micropenis is caused either by a defect in androgen synthesis, conversion to Dihydrotestosterone, or action due to mutant androgen receptor. Premature adrenarche is caused by excess of adrenal androgens.

Clinical case: A 6,5-year-old boy presented to our pediatric endocrinology clinic due to increased body weight and hyperthyreotropinemia. Physical examination revealed premature adrenarche with testicular volume 1,5 ml, micropenis (4cm, <-2 SDS) and acanthosis nigricans. His linear growth presented an acceleration the last 2 years from +0.85 to +1.81 SD and his bone age was advanced by 2 years with a statural height at -0.5 SD, not in accordance with the mean parental height (+0.90 SD). At the same time, his BMI was increased from +1,36 to +3,64 SDS.

Laboratory investigations for premature adrenarche with synacthen test revealed mild elevation of compound-S 15,4 ng/dl at 60’, which could be theoretically attributed to partial 11-β-hydroxylase deficiency (CYP11B1). DHEA was also elevated 2,1 ng/ml with an increased DHEA/Δ4 ratio at 20 (normal < 10) which could be explained in the case of partial 3-β-Hydroxysteroid dehydrogenase deficiency.

Method: Whole exome sequencing was preformed targeted to a gene panel related to premature adrenarche.

Results: A heterozygous mutation c.[1174C>T]+[1174C>T]; p.[Pro329Ser]+[Pro329Ser] in exon 1 in Androgen Receptor (AR) gene (X-linked) was found to the patient and his mother. The mutation, according to Human Gene Mutation Database, can cause disorder of sex development (DSD), partial androgen insensitivity syndrome (PAIS), infertility and hypospadias. Additionally, sequencing of the coding region of the P450 oxyreductase (POR) gene revealed a heterozygous mutation c.[642-5C>G] in exon 7, which in homozygosity can cause steroidogenesis disorder due to oxyreductase deficiency. This heterozygous POR mutation was found to the patient and his father.

Discussion: Our patient caries mutations in the AR and in POR genes. The AR mutation is obviously responsible for micropenis in our patient. CYP11B1 and 3β-Hydroxysteroid dehydrogenase genes were normal. POR deficiency is a disorder of steroidogenesis with phenotypic spectrum ranging from PCOS to ambiguous genitalia and glycocorticosteroid deficiency or even to classic Antley-Bixler syndrome (1).

Conclusion: The genetic and hormonal results in our case imply a role for POR in the CYP11B1 gene expression, which is reported for the first time to our knowledge.

1.

Concomitant Mutations in the P450 Oxidoreductase and Androgen Receptor Genes Presenting with 46,XY Disordered Sex Development and Androgenization at Adrenarche. J Clin Endocrinol Metab. 2010 Jul; 95(7): 3418-3427
MON-271 Identification of IGF-1 Variants in a Clinical Study of 307,000 Specimens: Discrepancies with General Population and Novel Discoveries
Authors: Motorykin Ievgen , McPhaul Michael John , Clarke Nigel J , Wu Zengru
Published: May 2020

High resolution accurate mass (HRAM) mass spectrometry (MS) is a highly specific and robust method for identifying and quantifying intact IGF-1. However, protein variants with mass-to-charge ratios differing from wild type (WT) are not included in quantification. Previously, we developed a naming convention for isotopic peaks, called the Isotopic Peak Index (IPi) that helps identify variants by comparing their IPis. This method cannot differentiate some variants; however, the relative retention time (rRT), which is defined as the difference between the chromatographic RT of a variant and that of the WT, may help in some cases. We report IGF-1 variants detected using rRT and IPi; we also compare expected and observed frequency of common variants A67T and A70T. For IPi, 4 variant groups (VGs), each monitored at a single m/z ratio, were identified to make detection of 15 variants more efficient. Variants within each VG could be distinguished if they had different IPis. To distinguish some variants in the same VG with the same IPi, we used rRT. We also developed a tandem mass-spectrometry (MS/MS) method that uses specific fragment ions generated during fragmentation to distinguish between the most abundant variants, A67T and A70T. Of the 307,269 samples we analyzed, 1,266 (0.4%) variants were identified. IPi identified variants with different indices and the rRT approach distinguished between pairs of variants that IPi could not (A38V vs A67V; R55K vs R36Q). The following variants (and their count) were identified: R50W/T4M/A67T/A70T (1,210), A67V (23), A38V (9), P66A (6), R36Q/R50Q (5), V17M/V44M (5), A67S (4), R55K/R56K (3), T29I/T41I (1), S34N (1), S33P (1), Y31H (1). We observed a different relative frequency of A67T and A70T variants than expected based on a general population ExAC DNA database. We expected to detect 2.1-fold more A67T than A70T counts. However, DNA sequencing of 74 samples in this study identified 1.6-fold more A70T occurrences (46) than A67T (28). Overrepresentation of A70T may suggest its clinical significance. The A38V variant was predicted to occur 5.1-times in the population studied, but it was detected 9 times. The A67V variant was not present in the ExAC database, but it was detected in 23 patients. We detected 2 variants that did not match WT or expected variants; DNA sequencing identified them as new variants (S33P, Y31H). DNA sequencing also identified 3 new variants (R50Q, R56K, T41I) at different positions than expected. Using a few test samples, the tandem MS technique has shown its ability to distinguish between A67T and A70T. It will be applied to this patient set. IPi and rRT can be used together to identify and differentiate IGF-1 variants. Such an approach may provide improved estimates of variant frequencies and identify new variants.
SUN-645 Cornus Officinalis Promotes IGFBP2 and Autophagy in Human 1.1B4 Pancreatic Cell Line as Revealed by Employing a Global Proteomic Approach via Mass Spectrometry
Authors: Tawfik Arielle Elizabeth , Guergues Jennifer , Stevens Stanley M , Burkhardt Brant Roger
Published: May 2020

Type 1 diabetes (T1D) results in the loss of pancreatic beta cells and subsequent loss of insulin production. Exogenous insulin is the only effective treatment, but there is still no cure or interventional therapy available to inhibit progression of T1D. Successful T1D interventional therapy must protect pancreatic beta cells from autoimmunity while enhancing beta cell survival and function. Our data suggests Cornus officinalis (CO) may be a candidate for interventional therapy to protect pancreatic beta cells from autoimmune attack and increase their function. CO has been used in traditional Chinese medicine (TCM) for over 2,000 years and has shown characteristics of anti-diabetic effects in vitro and in vivo but never examined in the application of T1D. Our prior publication (Mol. and Cell. Endo.2019:494:110491), has shown increased proliferation and protection against Th1 cytokine attack upon CO treatment using a human pancreatic beta cell line, 1.1B4. From this, we sought to define precise molecular mechanism by employing a global and phosphorylation mass spectrometry (MS) approach. We applied CO to 1.1B4 cells for 2, 6, 12, and 24h then collected the cell lysates for MS analysis. Our global MS analysis revealed a 12-fold increase in beta cell functional regulator, IGFBP2, at multiple time points. IGFBP2 has been shown to display a T2D protective effect and regulate glucose metabolism. The ingenuity pathway analysis program (IPA) predicted an increase in insulin starting at 2h and the NRF2-mediated oxidative stress pathway at 12h and 24h. Furthermore, NRF2 is an upstream regulator of P62 which was significantly hyperphosphorylated at multiple timepoints from our MS analysis. Nrf2 is responsible for activating antioxidant enzymes upon oxidative stress, which is caused by proinflammatory cytokines in T1D. P62 aids in this pathway by targeting proteins for autophagy upon oxidative stress in order to keep cellular homeostasis within beta cells rather than cells progressing through apoptosis. Autophagy is critical for beta cell function and survival as it promotes survival under beta cell stress which would otherwise lead to cell death. The recovery and protection of autophagy in beta cells of patients in the pre-diagnosed stages of T1D could provide a beneficial interventional therapy in order to delay or inhibit the onset of T1D. Altogether, our proteomic analysis revealed an increase in IGFBP2 and predicted an increase in the NRf2-mediated oxidative stress pathway upon CO induction. Further analysis will examine the IGFBP2 and Nrf2-mediated oxidative pathway as a mechanism of CO induced protective and proliferative effects in pancreatic beta cells.
SAT-272 Pituitary Macroadenoma Co-Secreting TSH and PRL Responsive to Cabergoline
Authors: Tirumalasetty Saritha , Galagan Robert , Lovre Dragana , David Julia
Published: May 2020

Background: Thyroid-stimulating hormone (TSH) secreting tumors (TSHoma) account for 0.5-2% of all pituitary adenomas with a prevalence of 1-2 cases per million, indicating that TSHomas are very rare. The majority of TSHomas solely secrete TSH however 9.7% co-secrete Prolactin (PRL). We are reporting a case of co-secreting TSH and PRL pituitary macroadenoma responsive to Cabergoline (CAB) Case: A 52 year old multiparous female presented with symptoms of galactorrhea and amenorrhea. Lab investigation revealed elevated PRL 73 ng/mL (n [normal] = 1-24), Total T3 305 ng/dL (n = 71-180), Free T4 (FT4) 2.37 ng/dL (n = 0.6-1.15), TSH 6.09 UIU/mL (n = 0.5-5.0), and α subunit 7.7 ng/mL. Estradiol was low at 16.9 pg/mL and FSH 6.3 MIU/mL LH 1.7 MIU/mL. Visual field testing showed a right nasal step. MRI imaging demonstrated a 21x24x32mm pituitary macroadenoma with optic chiasm distortion. Partial Transsphenoidal surgery (TSS) was performed and immunostaining of tumor tissue was positive for PRL and negative for other pituitary hormones. One month post-surgical MRI revealed 14x17x15mm residual tumor. One month post-op TFTs were normal: TSH 0.99 ng/dL, FT4 0.61 ng/dL; PRL decreased to 34.8 ng/mL. Six month post-op TSH increased to 5.86 UIU/mL, FT4 1.43 ng/dL, and PRL 44.7 ng/mL. Two years post-op TSH 8.06 ng/dL with elevated α subunit 3.4 ng/mL and PRL 56.8 ng/mL. Octreotide was then initiated for TSHoma treatment however she was unable to tolerate the medication due to diarrhea so was switched to CAB. After starting CAB at 0.5mg twice a week, residual sellar mass increased in size to 19.5x16x23mm with TFTs: TSH 5.66 UIU/mL, FT4 2.48 ng/dL. CAB dose was eventually uptitrated to 1mg twice a week. Repeat MRI showed slight decrease in pituitary lesion to 19x21x18mm and downtrending TFTs: TSH 2.28 UIU/mL, FT4 1.17 ng/dL. Discussion: In patients with pituitary tumors associated with elevated PRL and TSH, TSHoma should be part of the differential diagnosis. This patient’s initial lab evaluation with elevated PRL, TSH, FT4, Total T3, and α subunit confirm the diagnosis of a pituitary macroadenoma with co-secretion of PRL and TSH. Elevated PRL, TSH, FT4 and α subunit levels occurred 6 months after partial TSS resection with growing tumor size eventually requiring medical therapy. On CAB therapy, there were reductions in PRL, TSH, and FT4 levels as well as a decrease tumor size. This is the first reported case of a TSHoma responsive to CAB.
MON-234 síNdrome de InterrupcióN del Tallo Pituitario Que Se Presenta Como Amenorrea Primaria
Authors: Romero Fabiola , Arzamendia Sady Paola , Ferreira Dahiana , de Souza Claudia Neves , López Helen , Espinoza Grecia , Valinotti Elizabeth , Ayala Alejandro
Published: May 2020

Pituitary stalk interruption syndrome presenting as primary amenorrhea.

The pituitary stalk interruption syndrome is a rare congenital defect that is characterized by the absence or thinning of the pituitary stalk, an absent or ectopic posterior pituitary lobe, and hypoplasia or aplasia of the anterior lobe. The clinical presentation is variable.

It is usually diagnosed in the neonatal period due to the clinical manifestations that arise as a consequence of hormonal deficiencies. However some patients are diagnosed at a latter stage in life. Growth hormone deficiency it is observed in virtually all patients and can be associated to other anterior pituitary hormonal deficiencies. There is a high frequency of associated extra-pituitary malformations including those involving the central nervous system and the craniofacial structures.

We report the case of a 19-year-old woman with primary amenorrhea, lack of secondary sexual characteristics, short stature, low body mass index due to hypergonadotropic hypogonadism and growth hormone deficiency. The remaining pituitary hormones were normal. A pelvic ultrasound revealed orthotopic ovaries and uterus that were decreased in size. Her karyotype was normal. An MRI of the sellar region revealed an ectopic posterior pituitary lobe, and anterior pituitary hypoplasia with a thin pituitary stalk. The patient was treated with estradiol valerate and norgestrel as well as with growth hormone.

In conclusion, the pituitary stalk interruption syndrome is a rare form of congenital hypopituitarism that should be considered in cases of growth hormone deficiency and primary amenorrhea particularly in the presence of extra pituitary malformations involving the central nervous system.