ESPE Abstracts

Background: Genetic variants are identified in a small proportion (~10%) of patients with Congenital Hypopituitarism (CH), with variable associated phenotypes. We aimed to phenotypically characterise a large cohort of patients with genetically proven CH.Patients and methods: 1684 CH patients were screened (Sanger or whole exome sequencing) over a 20-year period (1998-2018) for mutations in genes regulating pitui...

Aim: To identify the distinctive features of GH Deficiency (GHD) and to assess the response to GH treatment (rhGH) in children with Septo-Optic-dysplasia (SOD) and Multiple Pituitary Hormone Deficiencies (MPHD).Methods: Retrospective longitudinal single centre study of children with SOD (n:171) and MPHD (n:53). GHD was diagnosed in patients with growth failure by an insufficient GH response (≤6.7 μg/l) to provocation (Insulin Induced Hypoglyca...

Background: Children with septo-optic dysplasia (SOD) and related disorders can present with either hypogonadotropic hypogonadism or precocious puberty. This phenotypic variability remains unexplained.Objective and hypotheses: To compare pubertal characteristics of SOD with isolated congenital hypopituitarism (CPHD) and optic nerve hypoplasia (ONH).Method: Retrospective longitudinal data collection from 259 patients with: SOD (...

Introduction: Septo-optic dysplasia (SOD) is characterized by a combination of midline forebrain, pituitary and eye abnormalities. We aimed to evaluate endocrine features of patients with SOD, and multiple pituitary hormone deficiencies (MPHD).Design: Retrospective data were collected from 130 patients: 102 SOD and 28 MPHD followed at a single tertiary centre. SOD were divided into two groups: with pituitary hormone deficiencies (SOD+, n=83) and...

Background: Few studies have described the phenotypic spectrum of Septo-Optic Dysplasia (SOD). The aim of this study was to evaluate the range of H-P structural abnormalities and the endocrine morbidity of children with SOD and related disorders.Methods: Retrospective longitudinal single centre study of children with SOD (n:171), Multiple Pituitary Hormone Deficiency (MPHD) (n:53) and Optic Nerve Hypoplasia (ONH) (n:35).<p class="ab...

Background: Patients with congenital adrenal hyperplasia (CAH) are glucocorticoid deficient and require cortisol replacement to maintain homeostasis and prevent adrenal crises. Hydrocortisone dosing needs to be individualized because of variable cortisol clearance rates. Patients are thus prone to be either over or undertreated, both of which compromises final height.Objective and hypotheses: Performing 24-h cortisol profiling serially may allow for more...

Background: P450 oxidoreductase deficiency (PORD) is characterised by glucocorticoid and sex steroid deficiency and skeletal malformations, resembling Antley–Bixler syndrome (ABS, MIM 124015), a skeletal malformaton phenotype also present in patients with fibroblast growth factor receptor 2 mutations (FGFR2, MIM 176943). While genetic testing confirms both conditions, establishing the exact diagnosis on clinical grounds can be challenging.Objective ...

Background: Donohue syndrome (DS) is the most severe form of insulin-resistance due to autosomal recessive mutations in the insulin receptor gene. Typical features include pre-/postnatal growth impairment, hyperinsulinaemic hyperglycaemia with fasting hypoglycaemia, nephrocalcinosis, recurrent sepsis, little adipose tissue, soft tissue overgrowth, hirsutism, acanthosis nigricans and facial dysmorphism. However, additional comorbidities may be present, affecting prognosis.<...

Background: Donohue syndrome (DS) is the most severe form of insulin-resistance due to autosomal recessive mutations in the insulin receptor gene. Previous reports demonstrate a role for recombinant human IGF1 (rhIGF1), however optimal treatment strategy remains unclear.Case series: Four males with DS have been treated with bolus rhIGF1 (see table below). They had no IGF1 response on an IGF1 generation test. No long-term side effects of rhIGF1 were repor...

Background: A mutation in EIF2S3 (NM_001415; Xp22.11) was previously associated with microcephaly and developmental delay in a single pedigree. EIF2S3 encodes the eukaryotic translation initiation factor 2 subunit 3 (eIF2γ), the largest of three EIF2 subunits. EIF2 initiates protein synthesis by forming a ternary complex with GTP and initiator methionyl-tRNA which then binds to the 40S ribosomal subunit, enabling scanning of mRNA from the 5′ end to...