Multiple pituitary hormone deficiency caused by Pit-I mutation and the challenges of management in a developing country

Background: In most developing countries, childhood endocrine disorders are not as common as infections but they do occur. Multiple pituitary hormone deficiency (MPHD) is a known cause of familial short stature. This is very rarely diagnosed in Nigerian children. We describe the challenges of diagnosis and management of childhood endocrine conditions in a developing economy using a ten year old Nigerian girl with MPHD as an illustration.Methods: Patient had auxological data suggestive of short stature. In order to make a definitive diagnosis, pituitary function tests were carried out in the United Kingdom.Results: Biochemical tests revealed growth hormone (GH) deficiency, Thyroid Stimulating Hormone (TSH) deficiency, decreased prolactin (PRL) level, normal cortisol and gonadotrophins. Her DNA analysis identified PIT-1 mutation in exon-6. She was placed on recombinant GH and thyroxine with evidence of catch up in height.Conclusions: There were challenges to management such as, inadequate facility for diagnosis, huge cost of treatment and little awareness about childhood endocrine conditions amongst health workers in a developing economy.Keywords: Multiple pituitary hormone deficiency (MPHD), PIT-1 mutation, short stature, management, developing country

Management of the child born small for gestational age through to adulthood: A consensus statement of the international societies of pediatric endocrinology and the Growth Hormone Research Society

Objective: Low birth weight remains a major cause of morbidity and mortality in early infancy and childhood. It is associated with an increased risk of health problems later in life, particularly coronary heart disease and stroke. A meeting was convened to identify the key health issues facing a child born small for gestational age (SGA) and to propose management strategies. Participants: There were 42 participants chosen for their expertise in obstetrics, peri- and neonatal medicine, pediatrics, pediatric and adult endocrinology, epidemiology, and pharmacology. Evidence: Written materials were exchanged, reviewed, revised, and then made available to all. This formed the basis for discussions at the meeting. Where published data were not available or adequate, discussion was based on expert clinical opinions. Consensus Process: Each set of questions was considered by all and then discussed in plenary sessions with consensus and unresolved issues identified. The consensus statement was prepared in plenary sessions and then edited by the group chairs and shared with all participants. Conclusions: The diagnosis of SGA should be based on accurate anthropometry at birth including weight, length, and head circumference. We recommend early surveillance in a growth clinic for those without catch-up. Early neurodevelopment evaluation and interventions are warranted in at-risk children. Endocrine and metabolic disturbances in the SGA child are recognized but infrequent. For the 10% who lack catch-up, GH treatment can increase linear growth. Early intervention with GH for those with severe growth retardation (height SD score, < -2.5; age, 2-4 yr) should be considered at a dose of 35-70 mu g/kg center dot d. Long-term surveillance of treated patients is essential. The associations at a population level between low birth weight, including SGA, and coronary heart disease and stroke in later life are recognized, but there is inadequate evidence to recommend routine health surveillance of all adults born SGA outside of normal clinical practice

Communication with young people in paediatric and adult endocrine consultations: an intervention development and feasibility study

Background: Communication is complex in endocrine care, particularly during transition from paediatric to adult services. The aims of this study were to examine the feasibility of interventions to support young people to interact with clinicians. Methods: Development and evaluation of a complex intervention in 2 phases: Pre-intervention observational study; Intervention feasibility study. Purposive sample of recordings of 62 consultations with 58 young people aged 11-25 years with long-term endocrine conditions in two paediatric and two adult endocrine clinics. Proportion of time talked during consultations, number and direction of questions asked; Paediatric Consultation Assessment Tool (PCAT); OPTION shared decision making tool; Medical Information Satisfaction Scale (MISS- 21). Young people were invited to use one or more of: a prompt sheet to help them influence consultation agendas and raise questions; a summary sheet to record key information; and the www.explain.me.uk website. Results: Nearly two thirds of young people (63%) chose to use at least one communication intervention. Higher ratings for two PCAT items (95% CI 0.0 to 1.1 and 0.1 to 1.7) suggest interventions can support consultation skills. A higher proportion of accompanying persons (83%) than young people (64%) directed questions to clinicians. The proportion of young people asking questions was higher (84%) in the intervention phase than in the observation phase (71%). Conclusions: Interventions were acceptable and feasible. The Intervention phase was associated with YP asking more questions, which implies that the availability of interventions could promote interactivity

Next-generation sequencing reveals deep intronic cryptic ABCC8 and HADH splicing founder mutations causing hyperinsulinism by pseudoexon activation

Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc.Next-generation sequencing (NGS) enables analysis of the human genome on a scale previously unachievable by Sanger sequencing. Exome sequencing of the coding regions and conserved splice sites has been very successful in the identification of disease-causing mutations, and targeting of these regions has extended clinical diagnostic testing from analysis of fewer than ten genes per phenotype to more than 100. Noncoding mutations have been less extensively studied despite evidence from mRNA analysis for the existence of deep intronic mutations in >20 genes. We investigated individuals with hyperinsulinaemic hypoglycaemia and biochemical or genetic evidence to suggest noncoding mutations by using NGS to analyze the entire genomic regions of ABCC8 (117 kb) and HADH (94 kb) from overlapping ~10 kb PCR amplicons. Two deep intronic mutations, c.1333-1013A>G in ABCC8 and c.636+471G>T HADH, were identified. Both are predicted to create a cryptic splice donor site and an out-of-frame pseudoexon. Sequence analysis of mRNA from affected individuals' fibroblasts or lymphoblastoid cells confirmed mutant transcripts with pseudoexon inclusion and premature termination codons. Testing of additional individuals showed that these are founder mutations in the Irish and Turkish populations, accounting for 14% of focal hyperinsulinism cases and 32% of subjects with HADH mutations in our cohort. The identification of deep intronic mutations has previously focused on the detection of aberrant mRNA transcripts in a subset of disorders for which RNA is readily obtained from the target tissue or ectopically expressed at sufficient levels. Our approach of using NGS to analyze the entire genomic DNA sequence is applicable to any disease

Transgenic Potatoes for Potato Cyst Nematode Control Can Replace Pesticide Use without Impact on Soil Quality

Current and future global crop yields depend upon soil quality to which soil organisms make an important contribution. The European Union seeks to protect European soils and their biodiversity for instance by amending its Directive on pesticide usage. This poses a challenge for control of Globodera pallida (a potato cyst nematode) for which both natural resistance and rotational control are inadequate. One approach of high potential is transgenically based resistance. This work demonstrates the potential in the field of a new transgenic trait for control of G. pallida that suppresses root invasion. It also investigates its impact and that of a second transgenic trait on the non-target soil nematode community. We establish that a peptide that disrupts chemoreception of nematodes without a lethal effect provides resistance to G. pallida in both a containment and a field trial when precisely targeted under control of a root tip-specific promoter. In addition we combine DNA barcoding and quantitative PCR to recognise nematode genera from soil samples without microscope-based observation and use the method for nematode faunal analysis. This approach establishes that the peptide and a cysteine proteinase inhibitor that offer distinct bases for transgenic plant resistance to G. pallida do so without impact on the non-target nematode soil community

BCG Revaccination Does Not Protect Against Leprosy in the Brazilian Amazon: A Cluster Randomised Trial

BCG is a vaccine developed and used to protect against tuberculosis, but it can also protect against leprosy. In Brazil, children receive BCG at birth, and since 1996 a trial has been conducted to find out if a second dose of BCG administered to schoolchildren gives additional protection against tuberculosis. We use this trial to find out if such vaccination protects against leprosy. The trial was conducted in the Brazilian Amazon, involving almost 100,000 children aged 7–14 years who had received neonatal BCG. Half of them received a second dose of BCG at school, and the other half did not. We followed the children for 6 years and observed that there were as many new cases of leprosy in the vaccinated children as in the unvaccinated children. Therefore, we concluded that a second dose of BCG given at school age in the Brazilian Amazon offers no additional protection against leprosy

Age, period, and cohort analysis of regular dental care behavior and edentulism: A marginal approach

<p>Abstract</p> <p>Background</p> <p>To analyze the regular dental care behavior and prevalence of edentulism in adult Danes, reported in sequential cross-sectional oral health surveys by the application of a marginal approach to consider the possible clustering effect of birth cohorts.</p> <p>Methods</p> <p>Data from four sequential cross-sectional surveys of non-institutionalized Danes conducted from 1975-2005 comprising 4330 respondents aged 15+ years in 9 birth cohorts were analyzed. The key study variables were seeking dental care on an annual basis (ADC) and edentulism. For the analysis of ADC, survey year, age, gender, socio-economic status (SES) group, denture-wearing, and school dental care (SDC) during childhood were considered. For the analysis of edentulism, only respondents aged 35+ years were included. Survey year, age, gender, SES group, ADC, and SDC during childhood were considered as the independent factors. To take into account the clustering effect of birth cohorts, marginal logistic regressions with an independent correlation structure in generalized estimating equations (GEE) were carried out, with PROC GENMOD in SAS software.</p> <p>Results</p> <p>The overall proportion of people seeking ADC increased from 58.8% in 1975 to 86.7% in 2005, while for respondents aged 35 years or older, the overall prevalence of edentulism (35+ years) decreased from 36.4% in 1975 to 5.0% in 2005. Females, respondents in the higher SES group, in more recent survey years, with no denture, and receiving SDC in all grades during childhood were associated with higher probability of seeking ADC regularly (<it>P </it>< 0.05). The interaction of SDC and age (<it>P </it>< 0.0001) was significant. The probabilities of seeking ADC were even higher among subjects with SDC in all grades and aged 45 years or older. Females, older age group, respondents in earlier survey years, not seeking ADC, lower SES group, and not receiving SDC in all grades were associated with higher probability of being edentulous (<it>P </it>< 0.05).</p> <p>Conclusions</p> <p>With the use of GEE, the potential clustering effect of birth cohorts in sequential cross-sectional oral health survey data could be appropriately considered. The success of Danish dental health policy was demonstrated by a continued increase of regular dental visiting habits and tooth retention in adults because school dental care was provided to Danes in their childhood.</p