hrp0084fc14.2 | Puberty | ESPE2015

A Mutation in HS6ST1 Causes Self-limited Delayed Puberty

Howard Sasha , Poliandri Ariel , Cabrera Claudia , Barnes Michael , Wehkalampi Karoliina , Dunkel Leo

Background: Self-limited delayed puberty (DP) often segregates in an autosomal dominant pattern, suggesting that inheritance is conferred by a small number of genes. However, the underlying genetic background is mostly unknown. By comparison, many genes have been identified where loss-of-function mutations lead to hypogonadotropic hypogonadism (HH). Despite likely overlap between the pathophysiology of delayed puberty and conditions of GnRH deficiency, few studies have examine...

hrp0082p1-d2-216 | Reproduction (1) | ESPE2014

IGSF1 Variants in Boys with Familial Delayed Puberty

Joustra Sjoerd , Wehkalampi Karoliina , Oostdijk Wilma , Biermasz Nienke , Howards Sasha , Bernard Daniel , Maarten Wit Jan , Dunkel Leo , Losekoot Monique

Background: The immunoglobulin superfamily member 1 (IGSF1) gene encodes a plasma membrane glycoprotein enriched in pituitary and testes. Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism (CeH), macroorchidism, and delayed pubertal rise of testosterone despite normal timing of testicular growth. This syndrome was discovered in patients with CeH; therefore, it is presently unknown whether IGSF1 mutations also cau...

hrp0092fc8.5 | Pituitary, Neuroendocrinology and Puberty Session 1 | ESPE2019

LGR4-Wnt β-Catenin Signalling Directs GnRH Network Development, with Defects Leading to Self-Limited Delayed Puberty

Mancini Alessandra , Howard Sasha R. , Cabrera Claudia P. , Barnes Michael R. , David Alessia , Wehkalampi Karoliina , Vassart Gilbert , Cariboni Anna , Garcia Marie Isabelle , Guasti Leonardo , Dunkel Leo

Background: The initiation of puberty is dependent upon an augmentation of gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus. Development of the GnRH neuroendocrine network in embryonic life depends on coordinated migration of neurons from the vomeronasal organ in the nose to the forebrain. We have previously demonstrated that dysregulation in GnRH neuronal migration leads to delayed pubertal onset. Late puberty affects up to 2% of the ...

hrp0084ha1 | Mutations in IGSF10 cause Self-limited Delayed Puberty, via Effects on GnRH Neuronal Migration | ESPE2015

Mutations in IGSF10 cause Self-limited Delayed Puberty, via Effects on GnRH Neuronal Migration

Howard Sasha , Guasti Leonardo , Mancini Alessandra , David Alessia , Storr Helen , Metherell Louise , Sternberg Michael , Cabrera Claudia , Warren Helen , Barnes Michael , Wehkalampi Karoliina , Andre Valentina , Gothilf Yoav , Cariboni Anna , Dunkel Leo

Background: Timing of puberty is associated with height, cardiovascular health and cancer risk, with a significant public health impact. Previous studies estimate that 60–80% of variation in the timing of pubertal onset is genetically determined. Self-limited delayed puberty (DP) often segregates in an autosomal dominant pattern, but the underlying genetic background is unknown.Methods: We performed whole exome sequencing in 52 members of 7 families...

hrp0089p2-p003 | Adrenals and HPA Axis P2 | ESPE2018

Glucocorticoid Replacement Regimens in the Treatment of 21-hydroxylase Deficiency Congenital Adrenal Hyperplasia: A Systematic Cochrane Review

Ng Sze , Stepien Karolina

Background: Congenital adrenal hyperplasia (CAH) is an autosomal recessive condition which leads to glucocorticoid deficiency. During childhood, the main aims of treatment are to prevent adrenal crisis and to achieve normal stature, optimal adult height and to undergo normal puberty. In adults, the aims of treatment are to prevent adrenal crisis, ensure normal fertility and to avoid long-term consequences of glucocorticoid use. Current treatment regimens for CAH with glucocort...

hrp0089p3-p203 | GH & IGFs P3 | ESPE2018

Results of Mecasermin Treatment in Pediatric Patients Evaluated for Severe and Partial Primary Deficiency of IGF-1

Stozek Karolina , Bossowski Artur

Background: Severe primary deficiency of insulin-like growth factor-1 (IGFD) being characterized by growth failure and short stature in children, constitutes an indication to recombinant human IGF-1 (mecasermin) treatment. It is defined by serum insulin-like-growth factor-1 (IGF-1) levels less than or equal to 2.5 th percentile, height less than or equal to −3 S.D.S., normal growth hormone (GH) secretion and exlusion of secondary causes of IGFD.<p clas...

hrp0084p3-1125 | Pituitary | ESPE2015

Combined Pituitary Hormone Deficiency

Kot Karolina , Moszczynska Elzbieta , Szalecki Mieczyslaw

Background: Combined pituitary hormone deficiency (CPHD) may be congenital or acquired disorder, which affects more than one hormonal axis. Congenital hipopituitarism includes heterogenic group of disturbances. It may be result of mutations or deletions in genes for signaling and transcription factors responsible for pituitary development. The disorder might affect one or multiple family members. The age of appearance and intensity of the first hormone deficiency symptoms may ...

hrp0086p2-p383 | Gonads &amp; DSD P2 | ESPE2016

Thyroid Autoimmunity in Adolescent Girls with Polycystic Ovary Syndrome – Pilot Study

Zachurzok Agnieszka , Skrzynska Karolina , Gawlik Aneta , Malecka-Tendera Ewa

Relationship between polycystic ovary syndrome (PCOS) and thyroid autoimmunity has been recently suggested by several authors. Autoimmune thyroiditis (AIT) is the most prevalent autoimmune disease and link between AIT and PCOS has been reported in adult women. There is a hypothesis that functional autoantibodies could contribute to the development of PCOS. The aim of the study was to evaluate the prevalence of thyroid autoimmunity in adolescent girls with PCOS. Forty five adol...

hrp0092fc5.2 | Thyroid | ESPE2019

Lower Proportion of CD19+IL-10+ and CD19+CD24hiCD27+ IL-10+, but not CD1d+CD5+CD19+CD24+CD27+ IL-10+ B Cells in Children with Autoimmune Thyroid Diseases

Stozek Karolina , Grubczak Kamil , Marolda Viviana , Eljaszewicz Andrzej , Moniuszko Marcin , Bossowski Artur

Introduction: Hashimoto's thyroiditis (HT) and Graves' disease (GD) become increasingly common in children's population. Pathogenesis of autoimmune thyroid diseases (AITD) bases on coexistence of genetic predisposition and environmental triggers which finally drive to breakdown of immune tolerance. Many mechanisms in human body moderate process of inflammation. While some of them answer for up-regulation, some agents like B regulatory lymphocytes (...

hrp0086p2-p54 | Adrenal P2 | ESPE2016

Hyperandrogenism in a 12-year Old Girl with a Congenital Porto-Systemic Shunt and Congenital Hepatic Fibrosis

Danko Mikolaj , Kot Karolina , Szalecki Mieczysław , Moszczynska Elzbieta , Malinowska Anna

Background: Hyperandrogenism in children is associated with excessive adrenal or gonadal androgens secretion. The most common causes of androgens hypersecretion are PCOS, adrenal tumors, Cushing’s syndrome, CAH, and gonadal virilizing tumors. Within the last 15 years single case-reports of hyperandrogenism in female patients with congenital porto-systemic shunts were described in literature. The mechanism of such coincidence is unknown but the role of hyperinsulinism, imp...