Assessment of Nutritional Status in the Diagnostic Evaluation of the Child with Growth Failure.

Current clinical guidelines provide information about the diagnostic workup of children with growth failure. This mini-review focuses on the nutritional assessment, which has received relatively little attention in such guidelines. The past medical history, in particular a low birth size and early feeding problems, can provide information that can increase the likelihood of nutritional deficits or several genetic causes.

Improved growth with growth hormone treatment in children after hematopoietic stem cell transplantation.

Objective: Hematopoietic stem cell transplantation (HSCT) can be a curative treatment for malignant and nonmalignant diseases in children but is associated with significant late effects including growth failure. Growth hormone treatment (GHRx) is offered to improve growth, but limited data are available on its effect on adult height (AH). We aim to evaluate the effectiveness of GHRx.

[The diagnostic evaluation of tall stature in children].

In this case series, we describe four children and adolescents with tall stature or growth acceleration to illustrate the diagnostic evaluation of tall stature according to the new Paediatric Association of the Netherlands (NVK) Guideline on growth disorders. A 14-year-old girl with tall stature and a relatively late onset of puberty was diagnosed with idiopathic familial tall stature, and the patient decided not to opt for epiphysiodesis. A 14-year-old boy with prepubertal growth acceleration and a history of behavioural problems was diagnosed with Klinefelter syndrome.

Novel Clinical Criteria Allow Detection of Short Stature Homeobox-Containing Gene Haploinsufficiency Caused by Either Gene or Enhancer Region Defects.

Introduction: Short stature homeobox-containing gene (SHOX) haploinsufficiency is associated with short stature, Madelung deformity and mesomelia. Current clinical screening tools are based on patients with intragenic variants or deletions. However, recent discoveries showed that deletions of the enhancer elements are quite common.

A Proposal for the Interpretation of Serum IGF-I Concentration as Part of Laboratory Screening in Children with Growth Failure.

The serum insulin-like growth factor-I (IGF-I) concentration is commonly used as a screening tool for growth hormone deficiency (GHD), but there is no consensus on the cut-off limit of IGF-I standard deviation score (SDS) to perform GH stimulation tests for confirmation or exclusion of GHD. We argue that the cut-off limit is dependent on the clinical pre-test likelihood of GHD and propose a diagnostic strategy in which the cut-off limit varies between zero to -2 SDS.

IGSF1 Deficiency Results in Human and Murine Somatotrope Neurosecretory Hyperfunction.

Context: The X-linked immunoglobulin superfamily, member 1 (IGSF1), gene is highly expressed in the hypothalamus and in pituitary cells of the POU1F1 lineage. Human loss-of-function mutations in IGSF1 cause central hypothyroidism, hypoprolactinemia, and macroorchidism. Additionally, most affected adults exhibit higher than average IGF-1 levels and anecdotal reports describe acromegaloid features in older subjects.

Towards a Rational and Efficient Diagnostic Approach in Children Referred for Tall Stature and/or Accelerated Growth to the General Paediatrician.

Tall stature and/or accelerated growth (TS/AG) in a child can be the result of a primary or secondary growth disorder, but more frequently no cause can be found (idiopathic TS). The conditions with the most important therapeutic implications are Klinefelter syndrome, Marfan syndrome and secondary growth disorders such as precocious puberty, hyperthyroidism and growth hormone excess. We propose a diagnostic flow chart offering a systematic approach to evaluate children referred for TS/AG to the general paediatrician.

Towards a Rational and Efficient Diagnostic Approach in Children Referred for Growth Failure to the General Paediatrician.

Based on a recent Dutch national guideline, we propose a structured stepwise diagnostic approach for children with growth failure (short stature and/or growth faltering), aiming at high sensitivity for pathologic causes at acceptable specificity. The first step is a detailed clinical assessment, aiming at obtaining relevant clinical clues from the medical history (including family history), physical examination (emphasising head circumference, body proportions and dysmorphic features) and assessment of the growth curve. The second step consists of screening: a radiograph of the hand and wrist (for bone age and assessment of anatomical abnormalities suggestive for a skeletal dysplasia) and laboratory tests aiming at detecting disorders that can present as isolated short stature (anaemia, growth hormone deficiency, hypothyroidism, coeliac disease, renal failure, metabolic bone diseases, renal tubular acidosis, inflammatory bowel disease, Turner syndrome [TS]).

Phenotypic Features and Response to GH Treatment of Patients With a Molecular Defect of the IGF-1 Receptor.

Context: The phenotype and response to GH treatment of children with an IGF1R defect is insufficiently known.

Objective: To develop a clinical score for selecting children with short stature for genetic testing and evaluate the efficacy of treatment.

Design And Setting: Case series with an IGF1R defect identified in a university genetic laboratory.

Relation between Early Over- and Undertreatment and Behavioural Problems in Preadolescent Children with Congenital Hypothyroidism.

Objective: Congenital hypothyroidism (CH) per se, when not treated or undertreated, may lead to severe behavioural problems (cretinism), whereas overtreatment of CH seems associated with attention problems.

Design And Methods: For 55 CH patients, prospectively followed from birth until 11 years, parents rated the Child Behaviour Checklist and teachers the Teacher's Report Form at children's ages 6 and 11 years. We related scores regarding Attention, Delinquency, and Aggression (ADA scores, indicative for attention deficit hyperactivity syndrome, ADHD), and scores regarding Withdrawn, Anxious, Social, and Thought problems (WAST scores, indicative for autism) to the occurrence of over- and undertreatment in five age periods.

A mathematical model for predicting the adult height of girls with idiopathic central precocious puberty: A European validation.

Background: A previous single-center study established a mathematical model for predicting the adult height (AH) in girls with idiopathic central precocious puberty (CPP).

Objective: To perform internal and external validations by comparing the actual AH to the calculated AH established by this model and to update it.

Methods: The original formula, calculated AH (cm) = 2.

Management and consequences of postoperative fluctuations in plasma sodium concentration after pediatric brain tumor surgery in the sellar region: a national cohort analysis.

Purpose: Severe fluctuations in plasma sodium concentration and plasma osmolarity, including central diabetes insipidus (CDI), may have significant influence on postoperative morbidity and mortality after pediatric brain tumor surgery.The aim of this study was to describe the frequency, severity and neurological consequences of these fluctuations in pediatric brain tumor survivors.

Methods: A retrospective, multi-institutional chart review was conducted among all children who underwent brain tumor surgery in the sellar or suprasellar region in seven university hospitals in the Netherlands between January 2004 and December 2013.

Global Application of the Assessment of Communication Skills of Paediatric Endocrinology Fellows in the Management of Differences in Sex Development Using the ESPE E-Learning.Org Portal.

Background: Information sharing in chronic conditions such as disorders of/differences in sex development (DSD) is essential for a comprehensive understanding by parents and patients. We report on a qualitative analysis of communication skills of fellows undergoing training in paediatric endocrinology. Guidelines are created for the assessment of communication between health professionals and individuals with DSD and their parents.

Pituitary Adenoma Apoplexy in an Adolescent: A Case Report and Review of the Literature.

We present a 13-year-old boy who was admitted with complaints of a state of progressive sleepiness and a sudden headache with vomiting and fever. Laboratory testing showed hypoglycemia, multiple pituitary hormonal deficiencies, and an elevated C-reactive protein level. A cranial magnetic resonance imaging (MRI) showed an opaque sphenoid sinus and an intrasellar mass suggesting hemorrhage, so that we suspected pituitary apoplexy (PA) originating from a non-functioning adenoma, although a pituitary abscess could not completely be excluded.

Successful Growth Hormone Therapy in Cornelia de Lange Syndrome.

Cornelia de Lange syndrome (CdLS) is a both clinically and genetically heterogeneous syndrome. In its classical form, it is characterised by distinctive facial features, intra-uterine growth retardation, short stature, developmental delay, and anomalies in multiple organ systems. NIPBL, SMC1A, SMC3, RAD21 and HDAC8, all involved in the cohesin pathway, have been identified to cause CdLS.

Combined pituitary hormone deficiency due to gross deletions in the POU1F1 (PIT-1) and PROP1 genes.

Pituitary development depends on a complex cascade of interacting transcription factors and signaling molecules. Lesions in this cascade lead to isolated or combined pituitary hormone deficiency (CPHD). The aim of this study was to identify copy number variants (CNVs) in genes known to cause CPHD and to determine their structure.

Mutations in TBL1X Are Associated With Central Hypothyroidism.

Context: Isolated congenital central hypothyroidism (CeH) can result from mutations in TRHR, TSHB, and IGSF1, but its etiology often remains unexplained. We identified a missense mutation in the transducin β-like protein 1, X-linked (TBL1X) gene in three relatives diagnosed with isolated CeH. TBL1X is part of the thyroid hormone receptor-corepressor complex.

Vitamin D Deficiency in Pediatric Fracture Patients: Prevalence, Risk Factors, and Vitamin D Supplementation.

Objective: Although vitamin D levels are not routinely monitored in pediatric fracture patients, identification of children with a vitamin D deficiency may be clinically relevant because of the potential role of vitamin D in fracture healing. This study aimed to determine the prevalence of vitamin D deficiency in a pediatric fracture population and to identify risk factors for deficiency.

Methods: All pediatric patients (<18 years) who were treated for a fracture of the upper or lower extremity from September 2012 to October 2013 in the outpatient setting of a level one trauma center were included in this cross-sectional study.

Individualized treatment to optimize eventual cognitive outcome in congenital hypothyroidism.

Background: In congenital hypothyroidism (CH), age-specific reference ranges (asRR) for fT and thyrotropine (TSH) are usually used to signal over/under-treatment. We compared the consequences of individual fT steady-state concentrations (SSC's) and asRR regarding over-treatment signaling and intelligence quotient at 11 y (IQ) and the effect of early over-treatment with high L-T dosages on IQ.

Methods: Sixty-one patients (27 severe, 34 mild CH) were psychologically tested at 1.

Novel Leptin Receptor Mutations Identified in Two Girls with Severe Obesity Are Associated with Increased Bone Mineral Density.

Background: Recessive mutations in the leptin receptor (LEPR) are a rare cause of hyperphagia and severe early-onset obesity. To date, the phenotype has only been described in 25 obese children, some of whom also had altered immune function, hypogonadotropic hypogonadism, reduced growth hormone secretion, hypothalamic hypothyroidism or reduced adult height. We provide a detailed description of the phenotype of 2 affected girls to add to this knowledge.

IGSF1 Deficiency: Lessons From an Extensive Case Series and Recommendations for Clinical Management.

Context: Mutations in the immunoglobulin superfamily, member 1 (IGSF1) gene cause the X-linked IGSF1 deficiency syndrome consisting of central hypothyroidism, delayed pubertal testosterone rise, adult macroorchidism, variable prolactin deficiency, and occasionally transient partial GH deficiency. Since our first reports, we discovered 20 new families with 18 new pathogenic IGSF1 mutations.

Objective: We aimed to share data on the largest cohort of patients with IGSF1 deficiency to date and formulate recommendations for clinical management.