bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT-070 Nutritional Deficiency of Calcium Mimicking P Seudohypoparathyroidism
Authors: Lee Yoonji , Ahn Moon Bae , Lee Na yeong , Lee Seonhwa , choi Yujung , Kim Seulki , Jung Min-Ho , Suh Byung-Kyu 
Published: May 2020

Abstract
BACKGROUND: Childhood hypocalcemia in general is caused by problems associated with calcium absorption and excretion, parathyroid hormone (PTH) secretion, and vitamin D metabolism. Clinical manifestations can vary from asymptomatic hypocalcemia to life-threatening conditions including convulsions, tetany and laryngeal spasm. As many symptoms are nonspecific, laboratory tests are essential for diagnosis. Nevertheless, the causes of hypocalcemia may not be determined by simple interpretation of baseline calcium, phosphorus, alkaline phosphatase (ALP), PTH and calcidiol (25OHD).
Case presentation: We report a case of 11-month-old female with a generalized tonic type seizure with low serum calcium level (5.7 mg/dl), 25OHD (23.2 ng/mL) and calcitriol (1,25OH2D) (12.83 pg/mL). Serum phosphorus (5.9 mg/dL), ALP (209 mg/dL) were above normal range and PTH (484 pg/mL) was markedly elevated. She had a problem with weaning process after age of 5 months and milk powder was her main staple diet. Pseudohypoparathyroidism (PHP) was suspected due to slightly increased serum phosphorus, however Albright’s hereditary osteodystrophy manifestation was absent and no GNAS methylation defect was identified. Serum calcium was normalized by intravenous calcium-gluconate followed by oral calcium carbonate and vitamin D supplement. Two months of oral oral calcium carbonate and vitamin D supplementation alone normalized all laboratory results.
Conclusions: Severe nutritional deficiency of calcium could mimic laboratory findings of PHP, therefore clinical judgement should not be made solely on biochemical markers.
Keywords: Hypocalcemia, pseudohypoparathyroidism, rickets
제1저자: Yoonji Lee, Moonbae Ahn, Na yeong Lee, Seonhwa Lee, Yujung Choi, Seulki Kim, Shinhee Kim, Wonkyoung Cho, Kyoungsoon Cho, Minho Jung, and Byungkyu Suh*
Department of Pediatrics, College of Medicine, Catholic University of Korea
OR10-02 Diagnosis of Severe GH Deficiency in Newborns: New Reference Range for the Preterm and Confirmation of the GH Cut-Off
Authors: Binder Gerhard , Weber Karin , degree no , Rieflin Nora , degree no , Steinruck Louis , degree no , Franz Axel 
Published: May 2020

Abstract
Introduction
Inborn severe GHD is caused by rare disorders of pituitary morphogenesis or function and frequently associated with additional pituitary hormone deficiencies. Affected newborns commonly present with recurrent hypoglycemia; therefore early diagnosis and therapy is warranted. The GH content of the newborn screening card is a reliable indicator of severe neonatal GHD. Here, we studied the GH content in screening cards and the history of 25 newborns with severe GHD. In addition, we determined the reference range of the GH content in screening cards from 282 healthy preterm newborns.
Patients and Methods
Since 2010, a total of 110 screening cards from hospitalized ill newborns were sent to our laboratory for measuring GH content. Using a questionnaire we obtained relevant clinical information from senders in 61 cases. Severe GHD was defined by the presence of recurrent neonatal hypoglycemia with either a significant cerebral MRI morphology or two additional pituitary hormone deficiencies. In addition, the GH content of screening cards from 282 healthy newborns born preterm with a gestational age at birth from 34.0 to 37.9 weeks was prospectively analyzed. The GH concentration of the eluate from the screening card was measured by a highly sensitive ELISA (Mediagnost, Germany); the GH serum concentration was calculated.
Results
In 25 patients, the definition of severe GHD of the newborn was fulfilled; based on recurrent hypoglycemia in combination with ectopia of the neurohypophysis in 17, septum pellucidum agenesis plus opticus hypoplasia in two, severely hypoplastic pituitary gland in two, and combined TSH and ACTH deficiency with no cMRI findings in four newborns. Five newborns with severe GHD were preterm. The median GH concentration of the term newborns with severe GHD (n=20) was 3.9 µg/l (range; 1.1 to 11.8). This was significantly below the previously reported reference data from healthy term newborns (n=269) (median 16.4 µg/l; 95% reference range 7.0 to 39.4) (p&lt;0.001). Using ROC plot analysis a GH serum concentration of 7.0 µg/l was identified as cut-off with the highest accuracy (90.0% sensitivity and 98.7% specificity). The median GH concentration of the 5 preterm newborns with severe GHD was 7.7 µg/l (range; 2.1 to 9.9). The newly determined 95% reference range for healthy newborns born preterm with a gestational age from 34.0 to 37.9 weeks (n=282) spanned from 7.9 to 41.1 µg/l with a median of 20.3 µg/l.
Conclusions
A GH content below 7.0 ng/ml in the newborn screening card identified severe GHD with 90% sensitivity and 98.7% specificity. In preterm newborns, the lower limit of the 95% reference interval was by 0.9 µg/l higher than in term newborns. The newborn screening card is a valuable source for the diagnosis of GH deficiency in newborns and young infants.
OR12-02 When the Glucocorticoid Receptor Meets the Mineralocorticoid Receptor in the Nucleus of Human Cells
Authors: Petrillo Maria G , Jewell Christine M , Oakley Robert H , Cidlowski John A 
Published: May 2020

Abstract
Adrenal corticosteroids, such as glucocorticoids and mineralocorticoids, are indispensable for mediating response to stress, development, limiting inflammation, and maintaining energy and fluid homeostasis. These hormones exert their actions via binding to two closely related nuclear receptors, the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR). The GR has low affinity for corticosteroids, but is expressed in nearly every cell. In contrast, the MR shows a higher affinity for corticosteroids and its expression is largely confined to those tissues where electrolyte exchange and fluid balance are required. GR and MR act as ligand-activated transcription factors which, following interaction with co-regulators and DNA responsive elements, either promote or repress gene transcription. The affinity for the same ligands, structural homology, and binding to the same DNA regions suggest GR and MR can compensate for each other’s actions. Yet, there are specific glucocorticoid and mineralocorticoid-mediated responses indicating GR-MR functional diversity. To investigate this interplay, we developed U-2 OS (human osteosarcoma) cell lines stably expressing GR, MR, and both GR and MR (GRMR). Immunofluorescence analysis showed that treatment of these cell lines with 1 nM of the synthetic glucocorticoid dexamethasone (Dex) induced nuclear traslocation of GR and MR. Conversely, treatment with 1 nM of aldosterone (Aldo) promoted nuclear translocation of the MR only. Moreover, Proximity Ligation Assay revealed that, in the absence of ligand, GR associated with MR in the cytoplasm and, upon 1 nM Dex exposure, GR-MR dimers were detected in the nucleus of GRMR cells. Surprisingly, nuclear GR-MR dimers were also detected in the presence of Aldo, suggesting that it is necessary to activate at least one receptor to induce nuclear traslocation of the heterocomplex. To decipher the functional contribution of GR-MR dimers in the transcriptional response of GR to Dex and MR to Aldo, we performed RNA-seq in GR, MR, and GRMR cells treated with 1 nM of Dex or Aldo. Transcriptome analysis revealed that Dex-activated GR regulated the transcription of 6180 genes. Co-expression of MR resulted in a blunted Dex-mediated gene response which affected only 1608 genes, suggesting a functional antagonism of MR. Aldo-activated MR regulated the transcription of 1660 genes. However, co-expression of GR expanded the Aldo-mediated gene response to 3150 genes. Strikingly, 74% of these genes were also regulated by Dex via GR, suggesting that GR-MR dimers in the presence of aldosterone are able to mimic the glucocorticod transcriptional response. Our data suggest that the role of distinct GR and MR homo- and hetero-dimers is relevant for regulating gene expression. Dissecting the mechanism and investigating the cross-talk between GR and MR may be useful to understanding these two receptors in heath and disease.
OR10-04 Interpretation of Insulin-like Growth Factor-1 (IGF-1) Levels Following Administration of Somatrogon (a Long-acting Human Growth Hormone - hGH-CTP)
Authors: Fisher Dennis M , Pastrak Aleksandra , Choe John , Wajnrajch Michael Paul , Cara José 
Published: May 2020

Abstract
IGF-1 is often used as a biomarker to evaluate the efficacy and safety of hGH replacement therapy. Typically, the mean IGF-1 SDS level during the dosing interval, rather than the peak value, guides clinical decision-making: sustained mean values &gt; +2 may require hGH dose modifications. With long-acting formulations (administered weekly), the IGF-1 evaluation paradigm needs to take into account when the sample was obtained relative to the last administered dose. Previous studies with OPKO’s once weekly Somatrogon (hGH-CTP), demonstrated that IGF-1 SDS peaked ~ 48 hours post-dose and that values at ~ 96 hours best approximated the mean IGF-1 SDS throughout the dosing interval [1]. Data from the pivotal Phase 3 non-inferiority study comparing treatment with Somatrogon to Genotropin allowed further evaluation of the IGF-1 SDS analysis paradigm.
Enrolled subjects were randomized to receive treatment with either once weekly Somatrogon (0.66 mg/kg; N=109) or once daily Genotropin (0.034 mg/kg; N=115). IGF1 was sampled ~ five times during 52 weeks of treatment with Somatrogon, providing a total of 557 samples obtained after the first dose of Somatrogon. IGF-1 SDS values were calculated using Bidlingmaier’s equations [2].
Analysis of IGF-I SDS data from the Phase 3 study showed that the previously-developed model, with adjustments to two parameters (baseline IGF-1, EC50) and adapted to fit IGF-1 values in the absence of Somatrogon concentration data, fit the IGF-1 data for Somatrogon with minimal bias. This allowed prediction of IGF-1 SDS values at timepoints throughout the dosing interval as well as calculation of the mean value during a dosing interval. Of the samples obtained between 48–72 hours post-dose (representing peak IGF-1 SDS), approximately 17% had an IGF1 SDS &gt; +2. At 96 hours (corresponding to mean IFG-1 SDS), fewer than 2% of modeled values were &gt; +2. Mean IGF-1 SDS over the dosing interval was between -1 and +1 for all subjects.
These findings indicate that IGF-1 SDS values need to be interpreted in the context of when the sample was obtained relative to the last dose of Somatrogon. Our results indicate that samples obtained 96 hours post-dose best represent mean IGF-1 levels and that values obtained between 48–72 hours post-dose represent values closer to peak IGF-1 concentrations. In our Phase 3 study, of the 557 samples collected from 114 patients during the 12-month Somatrogon treatment period, fewer than 2% of the corresponding values at 96 hours postdose (estimated from a pharmacokinetic/pharmacodynamic model) had IGF-1 SDS levels &gt; +2.
1. Fisher DM, et al. Horm Res Paediatr 2017;87:324. 2. Bidlingmaier M, et al. J Clin Endocrinol Metab 2014;99:1712
OR26-01 Epinephrine Is Essential for Normal Renal Glucose Reabsorption via the Glucose Transporter GLUT2
Authors: Elsheikh Arwa Mahmoud , de Souza Cordeiro Leticia M , Devisetty Nagavardhini , Ebert Steven N , Chhabra Kavaljit H 
Published: May 2020

Abstract
Humans and mice with Melanocortin 4 receptor (MC4R) deficiency remain protected from hyperglycemia despite chronic obesity and insulin resistance. We have observed that elevated glycosuria in MC4R deficient mice protects them from hyperglycemia. Moreover, our results indicate that circulating epinephrine may couple MC4R signaling with kidney glucose reabsorption. However, the direct role of epinephrine in regulating kidney glucose reabsorption remains unclear. We hypothesize that epinephrine is essential for maintaining glucose homeostasis via kidney glucose reabsorption. To test this hypothesis, we performed oral glucose tolerance tests (OGTTs) and intraperitoneal insulin tolerance tests (ITTs) in phenylethanolamine-N-methyltransferase (Pnmt) knockout (KO) mice that specifically lack epinephrine but have normal norepinephrine levels. Pnmt KO mice exhibited reduced insulin sensitivity compared to their Wild-Type (WT) littermates (Area under the curve for ITT: 9,700±256 vs. 8,482±417 mg/dL.min, p&lt;0.05). Paradoxically, we observed improved rather than impaired glucose tolerance in Pnmt KO mice compared to their WT controls (Area under the curve for OGTT: 32,546±1,592 vs. 40,058±1,918 mg/dL.min, p&lt;0.05). To ascertain if Pnmt KO mice, like MC4R deficient mice, show elevated glycosuria, we quantified their 24 urine glucose levels after oral glucose (250 mg) challenge. Indeed, Pnmt KO mice demonstrated elevated glycosuria compared to their WT littermates (Urine glucose: Baseline, 24.63±2.2 vs. 11.14±0.82 mg/dl; post glucose challenge: 67.83±5 vs. 16.09±1.13 mg/dl, p&lt;0.001), again validating the phenotype similar to that of MC4R deficient mice. To determine the glucose transporters involved in mediating elevated glycosuria in the Pnmt KO mice, we measured the levels of different renal glucose transporters using western blot. We found that GLUT2 was decreased by ~26% in Pnmt KO mice compared to their WT littermates. Levels of other glucose transporters were not changed, indicating that suppression of renal GLUT2 mediates elevated glycosuria in the epinephrine deficient mice. We validated the direct effect of epinephrine on GLUT2 levels in vitro using mouse primary renal proximal tubule epithelial cells. Indeed, epinephrine selectively increased GLUT2, but did not affect other glucose transporters in the mouse kidney primary cells. Our findings establish the essential role of epinephrine in glucose reabsorption via the renal glucose transporter GLUT2. Therefore, modulating the renal adrenergic system, or, kidney-specific GLUT2 may afford alternative strategies to regulate glycosuria and ultimately mitigate diabetes.
MON-105 A Case Report of Neonatal Hyperinsulinism in an Infant with Turner Syndrome Successfully Treated with Diazoxide
Authors: Patterson Rebecca J , Komsky Danielle , D’Ambrosio Fabiola , Mantis Stelios 
Published: May 2020

Abstract
BACKGROUND: Only four previous cases of hyperinsulinemic hypoglycemia have been reported in association with Turner Syndrome. All of these cases involved young females with a mosaic form of Turner Syndrome involving a ring X chromosome; an abnormality found in just 16% of Turner Syndrome karyotypes. Two of these cases showed responsiveness to diazoxide which stabilized their blood glucose levels and allowed for a longer fasting tolerance.
Clinical Case: A 5 day old female who was born at 36 weeks and 1 day with Turner Syndrome was referred to pediatric endocrinology for persistent episodes of hypoglycemia. Patient was started on D10W with electrolytes at an outside hospital due to hypoglycemia and was transferred to the NICU at day of life 3. D10W was discontinued on day of life 5 due to adequate PO feeding and reassuring blood glucose readings. Blood glucose was monitored every 4 hours and infant continued to have episodes of asymptomatic hypoglycemia typically in the mid-low 40’s, with one episode of low blood sugar to 36 mg/dl. Due to a concern for hyperinsulinism, labs were drawn at a serum blood glucose of 46mg/dl. The infant was found to have a beta-hydroxybutyrate of 0.2 (0.0-0.8mmol/L) and insulin of 1.0 (2.0–19.6uIU/mL). Hyperinsulinism was thus confirmed by the presence of inappropriately low ketones and inappropriately normal insulin in the setting of hypoglycemia. We initiated the patient on 7.5mg diazoxide BID (5.9mg/kg/day total) and was highly responsive to diazoxide. After her third dose (36 hours into treatment), her hypoglycemia had resolved and blood sugar readings had normalized. Patient was discharged home with a glucometer and instructions for the mother to call if blood glucose was less than 60. The patient has been stable on diazoxide with no reported episodes of hypoglycemia. Interestingly, her genetic testing demonstrated a complex chromosomal microarray pattern on chromosome X, a mosaicism with 2 cell lines: 1 with monosomy X and 1 cell line with a normal X chromosome with a ringed X chromosome.
Conclusion:This is a case demonstrating the efficacy of diazoxide in the management of asymptomatic hyperinsulinemic hypoglycemia in a neonate with Turner Syndrome with a ring X chromosome.
References: Cappella M, Graziani V, Pragliola A, et al. Hyperinsulinemic Hypoglycaemia in a Turner Syndrome with Ring (X). Case Rep Pediatr 2015; 2015:561974.
SUN-393 The Impact of Micronutrients on Cellular Metabolism and Healthy Aging
Authors: Astrup Arne , Cena Hellas , Frei Balz , Hwalla Nahla C 
Published: May 2020

Abstract
Micronutrients are involved in nearly all cellular processes, inadequacies or deficiencies may accelerate cellular aging and increase risk for chronic diseases later in life.1 Optimizing micronutrient intake may help reduce the risk for developing certain age-related conditions/diseases, including osteopenia/osteoporosis,2 sarcopenia,3 falls,4 mild cognitive impairment,5 immunosenescence,6 impaired resilience,7 hypertension,8 cataracts,9 and age-related macular degeneration.10 The importance of calcium and vitamin D for maintaining bone health has been established,2 but these micronutrients may also be involved with muscle health and reducing the risk for falls and consequent bone fractures in later life.11 Vitamin D may also be involved in stress management and resilience.12 Vitamins C, D, and E, zinc, selenium, and other micronutrients are necessary for healthy immune system function,13,14 and vitamin E is important for cognition,15 immune competence,16 and eye health.10 Although these micronutrients are individually involved with these processes by acting as antioxidants, hormonal regulators of gene expression, or cofactors in enzymatic reactions, there are also important interactions between micronutrients to consider (eg, calcium/vitamin D in musculoskeletal health). Importantly, a significant proportion of the aging population does not meet the recommended intake of many micronutrients.17 Clinical trials on the benefits of micronutrient supplementation have not been conclusive, but adequate intake should be considered an essential component of comprehensive healthcare for older adults.
References
1. Ames BN. Proc Natl Acad Sci U S A. 2006;103:17589–94
2. Nieves JW. Am J Clin Nutr. 2005;81:1232s-9s
3. Stockton KA, et al. Osteoporos Int. 2011;22:859–71
4. Shahar D, et al. Ann Nutr Metab. 2009;54:59–66
5. Barnes JL, et al. Nutr Rev. 2014;72:707–19
6. Cabrera AJ. Pathobiol Aging Age Relat Dis. 2015;5:25592
7. Rucklidge JJ, Blampied NM. NZ J Psychol. 2011;40:51–7
8. de Paula TP, et al. Sci Rep. 2017;7:40751
9. Weikel KA, et al. Nutr Rev. 2014;72:30–47
10. Evans JR, Lawrenson JG. Cochrane Database Syst Rev. 2017;7:CD000254
11. Robinson SM, et al. Clin Nutr. 2018;37:1121–32
12. Bracha HS, et al. Am J Geriatr Psychiatry. 2004;12:544–5
13. Puertollano MA, et al. Curr Top Med Chem. 2011;11:1752–66
14. Prietl B, et al. Nutrients. 2013;5:2502–21
15. Parker RS. In: Stipanuk MH, Caudill MA, eds. Biochemical, Physiological, and Molecular Aspects of Human Nutrition. 3rd ed. St. Louis, MO: Elsevier Saunders; 2013:670–82
16. Maijo M, et al. Mech Ageing Dev. 2014;136–137:116–28
17. Bugel S, Frei B. Care Weekly. 2019;3:1–12
SUN-277 Pituitary Hyperplasia Due to Severe Primary Hypothyroidism: An Uncommon Manifestation of a Common Disease
Authors: Singh Abhilasha , German Massiell , Sharma Anu 
Published: May 2020

Abstract
Background Pituitary hyperplasia (PH) is a non-neoplastic increase in one or more cell subtype of the adenohypophysis. It is physiologically seen in pregnancy from resultant lactotroph hyperplasia and pathologically in organ dysfunctions that lead to loss of negative feedback on hypothalamus like primary hypothyroidism and primary adrenal insufficiency. Although primary hypothyroidism is common, PH is an under-recognized consequence of long-standing hypothyroidism. Case Description A 26-year-old female with class 3 obesity, type 2 diabetes mellitus, and primary hypothyroidism on replacement presented for evaluation of secondary amenorrhea. Two months prior to presentation, she underwent a brain MRI for new-onset headache which revealed diffusely enhancing homogenous pituitary tissue measuring 2.3 cm with upward lifting of the optic chiasm. Serum prolactin was elevated at 86.2 ng/ml (2.8-26 ng/ml). This was presumed to be secondary to a prolactinoma and cabergoline was started by the referring provider. Subsequent workup revealed elevated thyroid-stimulating hormone (TSH) at 494.11 mU/L (0.30- 4.00 mU/L) and a low free thyroxine (FT4) of 0.2 ng/dl (0.8-1.7 ng/dl). Other pituitary hormones were within normal limits. The visual field examination was normal. It was noted she had a persistently elevated TSH over the past five years. On further questioning, the patient ran out of levothyroxine replacement 6 months ago and had been generally non-adherent to therapy for years due to nausea. Improved medication adherence resulted in the normalization of prolactin and reduction in TSH level. Repeat MRI 2 months later revealed a reduction in her pituitary hyperplasia to 2.1 cm. Discussion In severe primary hypothyroidism, there is loss of negative feedback to the hypothalamus due to low circulating FT4 and triiodothyronine (T3) concentrations. As a result, there is stimulation of thyrotropin-releasing hormone (TRH) which promotes thyrotroph hyperplasia. A strong correlation exists between TSH concentration and the degree of pituitary hyperplasia. The typical MRI finding is a diffusely enhancing homogenous pituitary mass. Despite optic chiasm contact, physiologic pituitary hyperplasia rarely causes visual field defects. High concentrations of TRH stimulates prolactin release with resultant mild hyperprolactinemia. Although PH is reversible with therapy, rare cases with subsequent development of panhypopituitarism while on therapy have been reported in the setting of longstanding hypothyroidism. Very rarely, chronically untreated primary hypothyroidism can stimulate the growth of a thyrotroph adenoma. Long-term biochemical and radiological monitoring is therefore recommended until resolution. This case highlights the physiologic responses manifested in severe primary hypothyroidism and the fact that these changes improve with adequate replacement.