Screening for acid-labile subunit deficiency in patients with growth hormone deficiency at a tertiary pediatric endocrinology center

Introduction: Acid-labile subunit (ALS) is a glycoprotein, which is produced in the liver in response to growth hormone (GH), with its main role being the formation of a complex with insulin-like growth factor 1 (IGF-1) and IGF-binding-protein-3 (IGFBP-3) in order to extend their circulating half-life and thus support the action of GH. Acid-labile subunit-deficient patients are of research interest because of the unclear incidence of the condition among the short-statured population and the need of specific therapeutic approach.Aim: The aim of this study is to assess the prevalence of ALS deficiency in a cohort of patients with GH deficiency (GHD) followed up in a tertiary university pediatric endocrinology center.Design: The study participants were 71 children (76% boys, age range 2–18 years), diagnosed with GHD by 2 standard GH-stimulation tests (max GH < 10 ng/mL), on GH therapy, and at mean age at the time of collection of samples: 11.6 ± 3.3 years. Blood serum samples were collected from each patient during the routine visits at the center, and then were stored frozen at -80℃ in 0.5 mL aliquots until analysis.Results: Acid-labile subunit deficiency screening identified serum ALS levels with range from 2.2 to 60 mg/L, with a mean of 17.4 ± 8.7 mg/L. The mean ALS levels were significantly lower than the published ones from subjects without short stature but close to the levels in the referred for GHD patients (6.5 ± 4.8 mg/L). Very low ALS levels (< 4.0 mg/L) were detected in 3 (4.2%) of the patients. The low ALS levels corresponded with low SDSheight (-2.8 ± 1.2) and low SDSIGF-1 (-1.4 ± 1.0) before therapy. In one of the 3 patients, the ALS level (2.2 mg/L) was close to that in patients with IGFALS gene mutations (< 1.0 mg/L).Conclusion: The present results show the prevalence of ALS deficiency in the current GH treated cohort and support the evidence that investigation of ALS levels could be helpful in the differential diagnosis of growth disorders

Comparative analysis of the practices of diagnostics and treatment of short stature, established in the outpatient clinics of general practitioners from Pleven and Varna

Introduction: Normal growth of the child is an index of good health, but it is a limited in time process, and for this reason, timely diagnosis and start of treatment of children with short stature (SS) are crucial for achieving adequate adult height and good quality of life.Aim: The aim of the present interview is to study the knowledge of general practitioners (GPs) about growth disorders and to increase the informational level in the process of creating national referral criteria and algorithms for the management of children with SS.Materials and Methods: GPs from Pleven and Varna (n=40, mean age 54.5 ± 8.85 yrs, work experience 25.9 ± 8.8 yrs, working in urban settings – 75%, children in their practices 0-18 - 23 079) have completed a questionnaire with 20 questions. All interviewed GPs defined SS as a problem for children. Almost all of them (80%) indicated use of standards for growth evaluation. They claimed that they provided screening for early detection of SS and they knew where to send a child with growth deviation. The main cause of SS, according to GPs, is genetic predisposition (35%), and that both - GPs and parents, are active in diagnosis of SS (82.5%). However, GPs shared that they were faced with some difficulties in the diagnosis of SS because of the “unclear” path of the patient after directing him to a specialist and that was the reason some of the children with SS to remain undiagnosed.Conclusion: SS is a problem that GPs are conscious of, but there is a strong need of measurements for building the “route” of the patient with SS, starting from the first step – the general practitioner

Initial results from the treatment with growth hormone of short, small for gestational age children

Introduction: Growth is important indicator of a child`s health. According to the literature, every year between 3 and 7% children are born with birth length and/or weight less than the 10th percentile for the corresponding gestational age. From those born short for gestational age (SGA), one in every ten children cannot catch up in growth. Recently, these children are defined in the literature as “short, SGA children”. Namely, in those children, especially in those untreated, metabolic and cardiovascular changes can be seen with age. In Bulgaria there is still no reimbursement for growth hormone (GH) treatment of this indication, and treatment is supported by a nation-wide charity (The Bulgarian Christmas).Aim: The aim of this article is to assess patients born SGA, without catch-up growth, regarding the age at start of the treatment, duration and effect of growth hormone treatment.Patients and Methods: Patients’ data was collected retrospectively from the maintained VECRED record. Statistical analysis was conducted by means of the SPSS programme. The most important factors regarding growth hormone treatment efficacy were assessed.Results: Currently at the center there are 43 SGA patients with short stature at an average age of 10.3 ± 7.1 y (1.7–40.1), 26 (60.5%) at an average age of 10.3 ± 4.2 y (3.7–17.3) are treated with growth hormone and 17 (39.5%) are just followed. The average age when the GH treatment was initially started is 6.5 ± 3.7 y (1.4–12.1). The gender distribution of the group is nearly 1:1 (22 boys:21 girls). The most common specific diagnosis is Silver-Russell Syndrome (22, 51.2%), followed by Noonan syndrome (3, 6.9%), Di George Syndrome (2, 4.7%), Lowe syndrome, etc. On the average the treatment duration is 39.3 ± 30.2 months (4–120). From the start of the treatment until the current survey, the height of the patients has increased with 1.23 ± 1.8 SDS.Conclusion: Growth hormone treatment in short SGA children leads to good results and that is why it is currently an accepted standard worldwide. This is also confirmed by the current results