hrp0092s5.1 | Impact of Genomics on Growth | ESPE2019

Novel Insights into Genetic Disorders of Growth

Argente Jesús

Human growth is a very complex phenomenon that is influenced by genetic, hormonal, nutritional and environmental factors from fetal life throughout puberty. Although the GH-IGF axis clearly has a central role in this process, with specific actions on longitudinal growth, numerous other genes are also involved in determining stature. Indeed, genome-wide association studies have identified >600 variants associated with human height, but this still only explains a small fract...

hrp0092fc15.6 | Late Breaking Abstracts | ESPE2019

Leptin Influences the Down-Regulation of UCP-1 Expression in Brown Adipose Tissue During Negative Energy Balance

Barrios Vicente , Canelles Sandra , Frago Laura M. , Chowen Julie A. , Argente Jesús

Background: The GH/IGF-I axis is involved in metabolic control and studies suggest that IGF-I deficiency and subsequent changes in IGF-I signaling in brown adipose tissue (BAT) modifies its thermogenic capacity. Food restriction reduces thermogenic capacity in BAT, while leptin stimulates thermogenesis through uncoupling protein 1 (UCP-1) induction. Leptin and IGF-I maintain important crosstalk in different tissues, but whether these two hormones interact to r...

hrp0092fc8.2 | Pituitary, Neuroendocrinology and Puberty Session 1 | ESPE2019

Analysis of Hypothalamic Metabolic Circuits after Normalization of Body Weight in Mice That Had Been Obese Due to High Fat Diet Intake

Guerra-Cantera Santiago , Frago Laura , Ros Purificación , Canelles Sandra , Díaz Francisca , Freire-Regatillo Alejandra , Torrecilla-Parra Marta Marta , Argente Jesús , Chowen Julie A.

The obesity epidemic continues to be a dramatic problem in the developed world despite attempts to curtail its rise. Reducing energy intake and/or increasing energy expenditure can result in weight loss; however, if one returns to their poor lifestyle habits the previous weight is not only recuperated, but often surpassed.We hypothesized that although a normal body weight may be achieved, the hypothalamic circuits controlling appetite and energy expendit...

hrp0092fc8.4 | Pituitary, Neuroendocrinology and Puberty Session 1 | ESPE2019

Peripheral and Hypothalamic Alterations in the Insulin-like Growth Factor (IGF) System in Response to High Fat Diet-induced Weight Gain

Guerra-Cantera Santiago , Díaz Francisca , Ros Purificación , Freire-Regatillo Alejandra , Torrecilla-Parra Marta , Barrios Vicente , Frago Laura , Chowen Julie A. , Argente Jesús

The insulin-like growth factor (IGF) system is fundamental for physiological processes such as growth and metabolism. In addition, in the brain it regulates glucose metabolism and neuroprotection. The IGF axis can be altered by nutritional status, but little is known regarding the effects of specific dietary components on this system.Our aim was to examine how high-fat diet (HFD) and low-fat/high sucrose diet (LFHSD) intake affect the central and circula...

hrp0092fc14.3 | GH and IGF3 | ESPE2019

PAPP-A2 Deficiency Induces Sex-Specific Changes in Hydroxyapatite-(CaOH) Crystallinity and the Effects of IGF-1 on Bone Composition in Adult Mice

Vargas Antonio , Rubio Leticia , Rivera Patricia , Christians Julian , de Fonseca Fernando Rodríguez , Chowen Julie , Suárez Juan , Argente Jesús

Deficiency of pregnancy-associated plasma protein-A2 (PAPP-A2), a regulator of IGF-1 availability, causes postnatal growth failure in humans and mice, at least in part through dysregulation of bone size and density. The present study aimed to determine the effects of Pappa2 gene deletion and the response to recombinant murine IGF-1 (rmIGF-1) on femur microstructure and composition. Hydroxyapatite-related crystallography and ionic substitutions were analyzed by X-ray p...

hrp0092rfc14.1 | Adrenals and HP Axis | ESPE2019

PAPP-A2 Deficiency Results in Sex-Dependent Modifications in Hypothalamic Regulation of Energy Homeostasis

Rivera Patricia , Vargas Antonio , Bonsón Javier , Christians Julian , Rodríguez de Fonseca Fernando , Chowen Julie , Suárez Juan , Argente Jesús

Pregnancy associated plasma protein (PAPP)-A2 is an insulin-like growth factor (IGF) binding protein (BP) protease that regulates IGF-1 availability affecting postnatal growth. Mutations in human PAPP-A2 cause short stature and changes in bone size and mineral density. The present study aimed to characterize the effects of constitutive Pappa2 gene deletion on hypothalamic regulation of energy homeostasis in adult male and female mice. In addition to being sho...

hrp0092p1-100 | Pituitary, Neuroendocrinology and Puberty | ESPE2019

RNPC3 Mutations Associate Prolactin Deficiency and Ovarian Insufficiency, Expanding the Phenotype Beyond Isolated Growth Hormone Deficiency Type V (MIM#618860)

Martos-Moreno Gabriel Á. , Travieso-Suárez Lourdes , Pozo Jesús , Chowen Julie , Pérez-Jurado Luis A. , Argente Jesús

Background: The first three children reported to have biallelic mutations in RNPC3 presented with growth hormone (GH) deficiency and pituitary hypoplasia (MIM#618860). RNPC3 codes for a minor spliceosome protein required for U11/U12 small nuclear ribonucleoprotein formation and splicing of U12-type introns. The underlying mechanism causing GH deficiency in these patients is not fully understood. Moreover, whether the association of further ho...

hrp0092p2-129 | Fat, Metabolism and Obesity | ESPE2019

Characterization of Adherence to Follow-up and Therapeutical Outcomes in a Large Cohort of 1300 Patients with Obesity Visited in a Specialized Tertiaty Care Center

Martínez-Villanueva Julián , González-Leal Rocío , Argente Jesús , Ángel Martos-Moreno Gabriel

Background: Adherence to follow-up visits in children and adolescents with obesity is a key factor for successful therapeutic outcomes in these patients.Objective: To analyze the adherence to scheduled visits and drop-out rate and the anthropometric, metabolic and behavioral outcomes as a result of an intervention program in a large cohort of children and adolescents with obesity.Patients a...

hrp0092p1-376 | Growth and Syndromes (to include Turner Syndrome) (2) | ESPE2019

Noonan Syndrome (NS) Spectrum Panels should Include Mutations in LZTR1 Gene

Güemes Maria , Martín-Rivada Álvaro , Ortiz-Cabrera Nelmar Valentina , Martos-Moreno Gabriel Ángel , Pozo-Román Jesús , Argente Jesús

Background: A few patients with NS have been reported to harbour pathogenic mutations in LZTR1 gene. RAS regulation by LZTR1-mediated ubiquitination provides an explanation for the role of LZTR1 in human disease. Mutations in this gene could hence lead to NS phenotype. Three patients with mutations in this gene and compatible NS phenotype are herein described.Case 1: A 5 year-old boy with bilateral cryp...

hrp0092p2-239 | Pituitary, Neuroendocrinology and Puberty | ESPE2019

Radiation Therapy for Children with Medulloblastoma: Growth and Thyroid Sequalae

Corredor-Andres Beatriz , Jerónimo Dos Santos Tiago , Alonso José Antonio , Cañas Mª Teresa , Muñoz-Calvo Mª Teresa , Argente Jesús

Background: Medulloblastoma is the most common malignant pediatric brain tumor. Although survival has improved with oncological therapy, late effects such as endocrine consequences are common, especially growth failure and thyroid dysfunction.Methods: Children diagnosed with medulloblastoma in a pediatric hospital between 2004 and 2014 were studied and followed until 2019. Statistical analysis was performed to estimate t...