hrp0092fc13.3 | Adrenals and HP Axis | ESPE2019

YAP1-HIPPO Pathway as a Novel Prognostic Marker and Therapeutic Target for Pediatric Patients with Adrenocortical Tumors (ACT)

More Candy Bellido , Bueno Ana Carolina , Castro Margaret , Antonini Sonir

Background: There is no effective adjuvant therapy for patients with advanced ACT. YAP1, a HIPPO pathway effector, interacts with Wtn\beta-catenin pathway and plays a crucial role in the maintenance of postnatal adrenal cortex and regulates cell proliferation and apoptosis in several tissues. We recently showed that overexpression of YAP1 associates with worse prognosis in our cohort of pediatric ACT (pACT).Aim: To analy...

hrp0082p1-d3-20 | Adrenals & HP Axis (1) | ESPE2014

Salivary Cortisol as a Diagnostic Tool of Hypercortisolism in Primary Pigmented Nodular Adrenocortical Disease (ppnad)

Moreira Ayrton , Elias Paula , Bittar Marcelo , Martinelli Carlos Eduardo , Antonini Sonir , Castro Margaret

Background: Hypercortisolism due to PPNAD may be cyclical, atypical and may develop suddenly or progressively.Objective and Hypotheses: The performance of salivary cortisol (SF) in this rare cause of Cushing’s syndrome (CS) is lacking.Method: Ten patients (nine F/one M) with PPNAD (two sporadic; eight Carney complex) were evaluated. Among these, six had CS family history, while in two the diagnosis was confirmed by germline PR...

hrp0082p2-d1-585 | Thyroid | ESPE2014

Subclinical Hypothyroidism is Associated with Low IGF1 Levels and Decreased Growth Velocity

Bellini Helena , Maciel Lea , Custodio Rodrigo , Milani Soraia , Paula Mariana , Antonini Sonir , Liberatore Raphael , Martinelli Carlos

Background: Subclinical hypothyroidism (SH) is defined as normal tyrosine levels in the presence of TSH concentrations between 5 and 10 mU/ml. The impact of SH on IGF system and growth of infants remains unknown.Objective and hypotheses: To evaluate IGF1, IGFBP3 levels and growth velocity (GV) of infants with SH.Method: 98 children up to 36 months of age, recalled due to a TSH >5 mU/ml in the neonatal screening test, were divid...

hrp0084p1-2 | Adrenal | ESPE2015

Ontogeny of the Synchronisation between Adrenal Clock Genes, Adrenal Steroidogenesis-Related Genes and the Circadian Rhythm of the HPA Axis in Rats

Ruiz Silvia , Martins Clarissa , Castro Margaret , Antonini Sonir , Martinez Edson , Moreira Ayrton

Introduction: The circadian rhythmicity of the hypothalamic–pituitary–adrenal (HPA) axis depends on the synchronization of the clock molecular systems in the suprachiasmatic nucleus and in the adrenals. When and how this process occurs in the adrenal is unknown.Objective: To assess the ontogeny of daily variation of the expression of the adrenal clock genes (Clock, Arntl, Per1, Per2, Per3, Cry1, Cry2, Rora, and Nr1d1), steroid...

hrp0089p1-p024 | Adrenals and HPA Axis P1 | ESPE2018

Gonadotropin-Dependent Pubertal Disorders are Common in Patients with Virilizing Adrenocortical Tumors in Childhood

Stecchini Monica F , Braid Zilda , More Candy B , Aragon Davi C , Castro Margaret , Moreira Ayrton C , Antonini Sonir R

Background: In pediatric patients with adrenocortical tumors (ACT), morbidity and mortality rates have been extensively evaluated. However, there are almost no data on the late consequences of early exposure to high androgen levels on pubertal development and on final height (FH) in these patients.Objective: To investigate the impact of early exposure to androgen excess on gonadotropin-dependent pubertal development and on final height (...

hrp0092rfc13.4 | Adrenals and HP Axis | ESPE2019

Loss-Of-Function NNT Mutations Impair Antioxidants Mechanisms and Decreases Cortisol Secretion in Patients with Famililar Glucocorticoid Deficieny

Faccioli Bodoni Aline , Coeli-Lacchini Fernanda , Gebenlian Juliana , Sobral Lays , Moreira Ayrton , Elias Lucila , Silva Wilson , de Catro Margaret , Leopoldino Andréia , Antonini Sonir

Background: The mitochondrial enzyme nicotinamide nucleotide transidrogenase (NNT) is essential in the antioxidant defense mechanisms and appears to be essential to the stages of adrenal steroidogenesis that occur inside the mitochondria.Aim: To characterize how mutations in NNT gene impair adrenal steroidogenesis resulting in familial glucocorticoid deficiency (FGD).Methods: Genom...

hrp0086p1-p726 | Pituitary and Neuroendocrinology P1 | ESPE2016

Time Course of Central Precocious Puberty Development Caused by an MKRN3 Gene Mutation: A Prismatic Case

Stecchini Monica , Macedo Delanie , Reis Ana Claudia , Abreu Ana Paula , Moreira Ayrton , Castro Margaret , Kaiser Ursula , Latronico Ana Claudia , Antonini Sonir

Background: Loss-of-function mutations in the imprinted gene MKRN3 represent the most common known genetic defects associated with central precocious puberty (CPP). The penetrance of these mutations remains to be established. To date, all reported individuals with MKRN3 mutations were already in puberty or postpubertal and were identified retrospectively.Objective and hypotheses: To report the first case of a prepubertal child with an MKRN3 muta...

hrp0084p2-400 | GH & IGF | ESPE2015

Regulation of IGF1R mRNA Expression by GnRH Agonist may be Involved in the Decrease of Height Velocity During Central Precocious Puberty Therapy

De Paula Mariana Sarti , Ricco Rafaela , Custodio Rodrigo , Milani Soraya , Atique Patricia , Moreira Ayrton , Antonini Sonir , Liberatorejr Raphael , Martinelli jr Carlos

Background: Growth spurt is a major event in central precocious puberty (CPP). GnRH analogue (GnRHa) therapy inhibits gonadal axis and decreases height velocity. However, serum IGF1 and IGFBP-3 remain high as before therapy. Reports on IGF type 1 receptor (IGF1R) in CPP are yet unavailable.Aim: To study IGF1R mRNA expression in girls with CPP before and during GnRHa therapy.Methods: 34 girls with CPP were studied. Sixteen of them (...

hrp0084fc1.2 | Adrenal | ESPE2015

Involvement of the Wnt/β-catenin Pathway, SF1, DAX1 and Stem/Progenitor Cell Markers in Paediatric Adrenocortical Tumors

Cavalcanti Marcelo M , Leal Leticia F , Coelli Fernanda B , Scrideli Carlos A , Molina Carlos A F , Tucci Silvio , Martinelli Carlos E , Yunes Jose A , Mastellaro Maria J , Moreira Ayrton C , Ramalho Leandra N , Castro Margaret , Antonini Sonir R

Background: Activation of the Wnt/β-catenin pathway is frequent in adrenocortical tumors (ACTs). This pathway and DAX1, a negative regulator of SF1 expression, control adrenal stem/progenitor cells, which can be involved in ACTs formation.Objective: To analyse the association between the Wnt/β-catenin pathway and the expression of a stem cell marker (NANOG), STAT3, DAX1 and SF1 in ACTs.Methods: Patients:...

hrp0082fc11.1 | Pituitary | ESPE2014

Abnormal Sonic Hedgehog Signalling in Adamantinomatous Craniopharyngiomas and its Association with CTNNB1/β-Catenin Mutations

Gomes Debora C , Jamra Soraya A , Leal Leticia F , Colli Leandro M , Juca Carlos E , Campanini Marina L , Oliveira Ricardo S , Martinelli Carlos E , Elias Paula C L , Saggioro Fabiano , Machado Helio R , Moreira Ayrton C , Serafini Luciano N , Castro Margaret , Antonini Sonir R

Background: The sonic hedgehog pathway (SHH) regulates CNS development and mutations or abnormal expression of the SHH pathway genes have been identified in epithelial tumors. SHH pathway interacts with Wnt/β-catenin signalling. To date, CTNNB1/β-catenin mutations are the sole molecular abnormality found in adamantinomatous craniopharyngiomas (ACPs).Objective and Hypotheses: To analyze the expression pattern of SHH pathway genes in ACPs and its...