______________________________________ P1-d1-164 Adrenals and HPA Axis 1 Arterial hypertension in children: alterations in mineralocorticoid and glucocorticoid axis and their impact on pro-inflammatory, endothelial damage, and oxidative stress parameters Carmen Campino1; Rodrigo Bancalari2; Alejandro Martinez-Aguayo2; Poster Presentations Marlene Aglony2; Hernan Garcia2; Carolina Avalos2; Lilian Bolte2; Carolina Loureiro2; Cristian Carvajal1; Lorena Garcia3; Sergio Lavanderos3; Carlos Fardella1 1Pontificia Universidad Catolica, Endocrinology, and Millennium Institute of Immunology and Immunotherapy, Santiago, Chile; 2Pontificia Universidad Catolica, pediatrics, Santiago, Chile; 3Universidad de Chile, School of Chemical Sciences, Santiago, Chile Background and aims: The pathogenesis of arterial hypertension and its impact and determining factors with respect to cardiovascular damage in chil- dren is poorly understood. We evaluated the prevalence of alterations in the mineralocorticoid and glucocorticoid axes and their impact on pro-inflam- matory, endothelial damage and oxidative stress parameters in hypertensive children. Methods: 306 children (5-16 years old); Group 1: Hypertensives (n=111); Group 2: normotensives with hypertensive parents (n=101); Group 3: normotensives with normotensives parents (n= 95). Fasting blood samples were drawn for hormone measurements (aldosterone, plasma renin activity (PRA), cortisol (F), cortisone (E)); inflammation vari- ______________________________________ ables (hsRCP, adiponectin, IL-6, IL-8, TNF-α); endothelial damage (PAI-I, P1-d1-163 Adrenals and HPA Axis 1 MMP9 and MMP2 activities) and oxidative stress (malondialdehyde). Famil- The role of S-palmitoylation of human ial hyperaldosteronism type 1 (FH-1) was diagnosed when aldosterone/PRA ratio >10 was associated with the chimeric CYP11B1/CYP11B2 gene. The glucocorticoid receptor in mediating the non- 11β-HSD2 activity was considered altered when the F/E ratio exceeded the genomic actions of glucocorticoids mean + 2 SD with respect to group 3. Nicolas C. Nicolaides1; Michael M. Roberts1; Tomoshige Kino2; Comparison between the groups was done by Kruskal-Wallis Test. Eleni Katsantoni1; Amalia Sertedaki3; George P. Chrousos3; Results: HF-1 was only detected in group 1; 4/115 children (3.4%). The Evangelia Charmandari3 F/E ratio was elevated (>4.3) in Group 1= 18/115 (15.6%); Group 2= 5/101 1Biomedical Research Foundation of the Academy of Athens, Division (4.9%) and Group 3= 5/95 (5.3%). of Endocrinology and Metabolism, Athens, Greece; 2National Institutes The comparison between groups 1, 2 and 3 showed differences in levels of F of Health, Unit on Molecular Hormone Action, Eunice Kennedy (ug/dl): 9.9[6.7-14.4]*, 8.5[6.2-11.1], 8.4[6.3-10.4]; F/E ratio: 2.9[2.2-3.9]*, Shriver National Institute of Child Health and Human Development, 2.8[2.2-3.3], 2.6[2.0-3.2]; hsCRP (mg/L): 1.2[0.4-2.3]*,**, 0.5[0.2-1.6], Bethesda, Maryland, United States; 3University of Athens Medical 0.5[0.2-1.3]; PAI-I (ng/ml): 22.2[13.4-31.7]*, 18.8[9.8-27.3], 14.9[8.9-23.3] School, Division of Endocrinology and Metabolism, First Department of and MMP-9: 2.2[1.3-3.0]*, 1.8[1.2-2.5], 1.6[1.2-2.3].*p<0.05 group 1 vs Pediatrics, Athens, Greece group 3, **p<0.05 group 1 vs group 2. Conclusions: In hypertensive children, HF-1 and deficient 11β-HSD2 activ- Background: In humans, glucocorticoids (GCs) regulate a broad spectrum ity were detected in addition to increases in inflammation, subclinical and of physiologic functions and exert both genomic and non-genomic actions endothelial damage. These results highlight the importance of blood pressure through their ubiquitously expressed glucocorticoid receptor (hGR). The rap- measurement in the child population. id non-genomic actions of GCs are likely to be mediated by membrane hGRs that transduce the glucocorticoid signal via activation of kinases. S-palmi- toylation plays an important role in plasma membrane (PM) localization and ______________________________________ occurs through a highly conserved 9 amino acid motif in the ligand-binding P1-d1-165 Adrenals and HPA Axis 1 domain (LBD) of steroid receptors. A highly homologous sequence is present The effect of anastrozole on the predicted in the LBD of the hGRα protein, suggesting that the hGR might also undergo height of obese boys with premature S-palmitoylation. Objective and hypotheses: To determine the role of S-palmitoylation of hGR adrenarche, delayed gonadarche and in mediating rapid glucocorticoid signaling following translocation and bind- advanced bone age ing to the PM. Nordie Anne Bilbao; Mariano Castro-Magana Methods: In vitro studies were performed to determine the specific residues Winthrop University Hospital, Pediatric Endocrinology, Mineola, United within the 9 amino acid motif of the LBD of hGRα that are crucial for rapid States glucocorticoid signaling. Specifically, we determined whether mutation of the amino acids at position -2, 0 and +5/6, relative to cysteine in the 9 amino Background: Premature adrenarche is the early onset of secretion of adrenal acid motif, significantly reduces localization of the receptor to the PM, S- androgens. The adrenal androgens dehydroepiandrosterone (DHEA), dehy- palmitoylation, association with caveolin-1, and MAPK and PI3K activation. droepiandrosterone sulfate (DHEAS), and androstenedione are converted to Results: Both the wild-type and the mutant receptors hGRαY663A, estrogens by the enzyme aromatase. There is a significant association of pre- hGRαC665A and hGRáLL670/671AA showed similar distribution to the PM. mature adrenarche with obesity. The increased aromatase activity in obesity Addition of 2-bromopalmitate, an S-palmitoylation inhibitor, did not prevent enhances estrogen production. Since estrogens are responsible for skeletal PM localization of the receptor or colocalization with caveolin-1. Compared maturation, its increase can result in an advanced bone age and a decreased with the wild-type hGR, all hGR mutant receptors resulted in decreased acti- height prediction. Estrogens exert a negative feedback to the pituitary LH and vation of MAPK signaling from 60 min onwards. A similar reduction in wild- FSH secretion, thus causing delayed gonadarche. Aromatase inhibitors, which type GR-induced MAPK signaling at 60 min was observed after treatment block the aromatase enzyme, decrease estrogens and increase testosterone, with 2-bromopalmitate. resulting in slower progression of skeletal maturation, and possibly increased Conclusions: S-palmitoylation facilitates sustained activation of the MAPK predicted height. pathway. Further studies are required to confirm that the hGR protein medi- Objective and hypotheses: We hypothesize that treatment with anastrozole ates this effect through the 9 amino acid motif in the LBD. increases the predicted height of obese boys with premature adrenarche, who have delayed gonadarche and advanced bone age. We aim to compare the __________________________________________________ __________________________________________________ ___________________ 51st Annual Meeting of the ESPE Horm Res 2012;78(suppl 1) 47 Downloaded by: 198.143.45.33 - 12/22/2015 7:55:39 PM predicted height at baseline and after two years of treatment with anastrozole seminiferous tubules may lead to obstructive azoospermia and irreversible in these boys. damage of the surrounding testicular tissue.Therefore, it may be important to Population and methods: The study is conducted on twenty boys 8-12 years detect and treat the tumours in an early stage. Ultrasound is a good method old diagnosed with prior premature adrenarche from years 2006 through for detection and follow-up of TART, especially when they are not palpable 2011, who received anastrozole, 1 mg/day, for two years. These boys also by physical examination. TART is already detected in children, however the have advanced bone age, delayed gonadarche in relation to the bone age age of first detection is not known and screening of TART is not routinely and obesity (BMI +2 SDS). Predicted heights (determined from the Bayley- performed. Pinneau tables) at baseline and two years after treatment were obtained and Objective: Aim of our cross sectional study was to define the prevalence and compared using the paired t- test. age of first detection of TART in a group of 42 paediatric male CAH patients Results (Preliminary): There is a significant increase in the mean predicted age 0 – 19 years old. height of 6.8 cm two years after treatment with anastrozole compared to the Methods: All male classic CAH children who are regularly followed at our predicted height at baseline in obese boys with premature adrenarche, delayed outpatient pediatric endocrine clinic were included. Ultrasonographic evalua- gonadarche and advanced bone age (p=0.02). tion was performed by an experienced radiologist (KK) with a high-frequency Conclusions: Anastrozole increases the predicted height in obese boys with linear array transducer L 17 / 5 (17 MHz) in two directions (transversal and premature adrenarche, delayed gonadarche and advanced bone age. sagital). Results: Below the age of 10 years no TART were detected (16 patients). Above the age of 10 there was a clear increase in prevalence of TART: 10 – ______________________________________ 12 years 28% (2 of 7 patients), 13 – 14 years 50% (4/8), 15 – 16 years 75% P1-d1-166 Adrenals and HPA Axis 1 (3/4). Above the age of 16 TART were detected in 100% of the patients (7/7). Hair cortisol as a novel monitoring tool for The tumors