ESPE Abstracts

46,XY differences of sex development (46,XY DSD) comprise a very heterogeneous group of people amongst DSD. While some conditions are well characterized on the molecular level, e.g. androgen biosynthesis enzyme deficiency or DSD due to genetic variants in the androgen receptor, many 46,XY DSD patients lack a specific diagnosis, especially those people where gonadal development is affected. A specific diagnosis, however, is helpful to develop an individualized management progra...

Introduction: The metabolically healthy obese phenotype (MHOF) defines obese patients who have preserved insulin sensitivity and who do not have metabolic complications: lower risk of cardiovascular disease and type 2 diabetes in adulthood. Recent studies indicate that TMI (kg/m3) estimates the percentage of body fat more accurately than the BMI and it has been proposed to substitute the use of the BMI z-score values by those of the TMI. TMI values ...

Background: Steroidogenic factor 1 (encoded by the NR5A1 gene) is a transcriptional regulator of genes involved in gonadal development and steroidogenesis. Mutations in NR5A1 are associated with a wide phenotypic spectrum in 46,XY individuals ranging from partial/complete gonadal dysgenesis or anorchia, ambiguous genitalia, hypospadias, to infertility. However, little is known about the longitudinal course of endocrine markers for Sertoli and Leydig cell func...

Background: The approach to investigating a newborn with a suspected DSD is likely to vary between centres and may be influenced by local availability.Method: To explore the current diagnostic practice and needs, an international survey of 124 paediatric endocrinologists, identified through DSDnet and the I-DSD Registry, was performed in 2014.Results: A total of 77/124 (62%) clinicians, in 74 centres, from 38/42 (91%) countries res...

Background: Disorders (or differences) of sex development (DSD) are rare congenital conditions in which the development of chromosomal, gonadal, or anatomical sex is atypical. The luteinizing hormone/chorionic gonadotropin receptor (LHCGR) is important for male sex development. LHCGR mutations can cause Leydig cell hypoplasia, which is an autosomal recessive disorder.Objective and hypotheses: We found two heterozygous mutations in the LHCGR, a n...

X-linked hypophosphatemia (XLH) is the most common genetic disorder of phosphate homeostasis. It is caused by inactivating mutations in the PHEX gene, which encodes a phosphate regulating endopeptidase predominantly expressed in osteoblasts, osteocytes, and odontoblasts.In children there is a broad phenotypic spectrum of XLH ranging from isolated hypophosphatemia without clinical signs up to severe symptoms, such as rickets, extreme lower limb d...

Background: Pseudohypoparathyroidism (Albright hereditary osteodystrophy (AHO)) is a rare congenital disorder mainly affecting bone and thyroid metabolism as a result of resistance of parathyroid hormone (PTH) and thyrotropin (TSH), gonadotropins, growth hormone-releasing hormone (GHRH) and calcitonin in the target tissues. According to the consensus statement "Diagnosis and management of pseudohypoparathyroidism and related disorders" published in 201...

Background: Neonatal severe hyperparathyroidism (NSHPT) has been associated with inactivating mutations of the calcium-sensing receptor (CASR) gene. Impaired inhibition of PTH secretion by extracellular ionized calcium and decreased urinary excretion of calcium leads to severe hypercalcemia in the first days of life. Calcium responsiveness of the CaSR is amplified by type 2 calcimimetic agents like cinacalcet, which has been able to normalize PTH and calcium levels in cases of...

Background: 46, XY-disorders of sex development (DSD) are due to different causes like androgen insensitivity, gonadal dysgenesis, defects in testosterone metabolism and others. Exact diagnosis is mandatory prior to medical advice, therapeutic steps, or even surgical procedures. To show the difficulties of gender assignment before and also after a correct diagnosis we describe a patient who waited 35 years for the complete diagnosis, but was advised, treated and operated befor...

Background: Disorders related to an impairment in parathyroid hormone (PTH) signaling pathway are historically classified under the term pseudohypoparathyroidism (PHP), that now encompasses rare, related but highly heterogeneous diseases with demonstrated (epi)genetic causes. The actual classification is based on the presence or absence of specific clinical and biochemical signs together with an in vivo response to exogenous PTH and an in vitro assay of Gs&#9...