Pediatric Endocrine Disorders Research Articles

Experience With Store-and-Forward Consultations in Providing Access to Pediatric Endocrine Consultations in Low- and Middle-Income Countries.

Pediatric specialists are often unavailable in low- and middle-income countries. As part of multiple professional associations' efforts to improve access to endocrine expertise globally, a pediatric endocrine teleconsultation network was established on a store-and-forward teleconsultation platform to facilitate focused, language-appropriate advice that can be kept for future reference while bypassing real-time video-conferencing, and obviating the need for a scheduled appointment. User information was recorded, and quality statistics on network performance and qualitative evaluation by referring physicians were analyzed. Over a 3-year period, 81 referrers (88% from Haiti) and 13 pediatric endocrinologists registered onto the network and discussed 47 pediatric endocrine cases, exchanging a total of 412 messages for a median of 7 messages (IQR 5, 11) per case. Diagnoses spanned the spectrum of pediatric endocrine disorders. According to referrers, an appropriate expert was consulted and an answer provided sufficiently quickly in 100% of cases. The answer was well-adapted to their environment in 86%, and referrers were able to follow the advice given in 72%. All but one referrer found the advice helpful, it clarified the diagnosis in 88%, assisted with management in 93%, improved patient's symptoms in 77%, improved function in 77%, and was considered cost-saving in 50%. Perceived benefits of the consultations were academic instruction, setting-adapted advice beyond the scope of guidelines or textbooks, and advancement in the diagnostic process. Pediatric endocrine remote store-and-forward consultations in low- and middle-income countries may provide a reasonable alternative to face-to-face visits, providing clinical and educational benefit, and a potential for cost-saving.

Pattern of Paediatric Endocrine Disorders According to ICD-10 Classification in a Tertiary Centre in Southern Nigeria

Aim: To describe the spectrum of various endocrine disorders seen in children and adolescents in Port Harcourt over the period 2013-2017 using modified European Society of Paediatric endocrinology ICD -10 classification.
 Study Design: Descriptive, Cross sectional study.
 Place and Duration: Paediatric endocrinology Unit, Department of Paediatrics, University of Port Harcourt Teaching Hospital. Study was done with data from January 2013 to August 2017.
 Methods: A retrospective review of 178 patients with various endocrine diseases was reported. Data on biodata, clinical presentations and investigations with diagnosis were retrieved from the clinic and ward records and endocrine unit registers.
 Results: A total of 178 patients were seen with various endocrine disorders over the study period accounting for 4.5% of Paediatric specialist clinic consultations. There were 89(50.0%) females and 80(44.9%) males. Nine (5.1%) had genital ambiguity. The ages of patients ranged from 12days to 17years with a mean age of 6.9 ± 5.1years. The commonest endocrine disorders were pubertal disorders, diabetes mellitus, thyroid disorders and calcium phosphate metabolism and bone disorders in 34(17%), 27(14%) 23(12%), 22(11%) and 22(11%) respectively. Twenty two (11%) of the patients had obesity and 10(5%) had syndromes with endocrine features. Other disorders seen were sex development and gender disorders, testicular/male reproductive tract disorders, growth disorders (short stature) ovarian/female reproductive tract disorders, pituitary/ hypothalamic disorders and adrenal disorders in 17(9%), 17(9%) 10(5%),7(4%), 5(2.5%) and 3(1.5%) respectively. Type 1 DM remained the commonest type of DM. Most of the patients were of the middle social class (social class III). Challenges to management included high cost of investigations and drugs, high rate of loss to follow up.
 Conclusion: Pubertal disorders, type 1 Diabetes mellitus, thyroid disorders, calcium and phosphate metabolism and bone disorders and obesity were the commonest cases in our review. Most investigations were available in private laboratories with high cost of investigation leading to loss to follow up and continuation of care.

Artificial intelligence-assisted interpretation of bone age radiographs improves accuracy and decreases variability.

Radiographic bone age assessment (BAA) is used in the evaluation of pediatric endocrine and metabolic disorders. We previously developed an automated artificial intelligence (AI) deep learning algorithm to perform BAA using convolutional neural networks. We compared the BAA performance of a cohort of pediatric radiologists with and without AI assistance. Six board-certified, subspecialty trained pediatric radiologists interpreted 280 age- and gender-matched bone age radiographs ranging from 5 to 18years. Three of those radiologists then performed BAA with AI assistance. Bone age accuracy and root mean squared error (RMSE) were used as measures of accuracy. Intraclass correlation coefficient evaluated inter-rater variation. AI BAA accuracy was 68.2% overall and 98.6% within 1year, and the mean six-reader cohort accuracy was 63.6 and 97.4% within 1year. AI RMSE was 0.601years, while mean single-reader RMSE was 0.661years. Pooled RMSE decreased from 0.661 to 0.508years, all individually decreasing with AI assistance. ICC without AI was 0.9914 and with AI was 0.9951. AI improves radiologist's bone age assessment by increasing accuracy and decreasing variability and RMSE. The utilization of AI by radiologists improves performance compared to AI alone, a radiologist alone, or a pooled cohort of experts. This suggests that AI may optimally be utilized as an adjunct to radiologist interpretation of imaging studies to improve performance.

Paediatric Anti-Müllerian Hormone measurement: Male and female reference intervals established using the automated Beckman Coulter Access AMH assay.

SummaryObjectiveAnti‐Müllerian Hormone (AMH) concentration is high at birth in males, demonstrating the presence of functional testicular tissue in the prepubertal period, and acting as a useful marker in the investigation of paediatric reproductive disorders. AMH also provides a tool in the investigation of female virilization, premature ovarian failure and polycystic ovarian syndrome in childhood. Robust, assay‐specific paediatric AMH reference intervals are therefore required for clinical interpretation of results. The aim of this study was to derive age‐specific AMH reference intervals for males and females aged 0‐18 years.Design and PatientsPlasma samples were obtained from patients at Royal Manchester Children's Hospital and analysed for AMH using the automated Beckman Coulter Access AMH Assay. Patients under investigation for paediatric reproductive or endocrine disorders were excluded from the study.MeasurementsSeven hundred and 2 patient plasma samples (465 male, 237 female) were subject to AMH measurement, and results were analysed in order to derive continuous and discrete reference intervals for the paediatric age range.ResultsClear discrimination between male and female AMH results was evident in the prepubertal age range, with some overlap between the genders following pubertal onset.ConclusionsWe have derived age‐related reference intervals for plasma AMH in the paediatric age range (0‐18 years) using the automated Beckman Coulter Access AMH assay which will aid in the investigation of paediatric endocrine disorders such as disorders of sexual development.

A simple method for bone age assessment: the capitohamate planimetry

ObjectivesTo determine if the capitohamate (CH) planimetry could be a reliable indicator of bone age, and to compare it with Greulich-Pyle (GP) method.MethodsThis retrospective study included 391 children (age, 1–180 months). Two reviewers manually measured the areas of the capitate and hamate on plain radiographs. CH planimetry was defined as the measurement of the sum of areas of the capitate and hamate. Two reviewers independently applied the CH planimetry and GP methods in 109 children whose heights were at the 50th percentile of the growth chart.ResultsThere was a strong positive correlation between chronological age and CH planimetry measurement (right, r = 0.9702; left, r = 0.9709). There was no significant difference in accuracy between CH planimetry (84.39–84.46 %) and the GP method (85.15–87.66 %) (p ≥ 0.0867). The interobserver reproducibility of CH planimetry (precision, 4.42 %; 95 % limits of agreement [LOA], −10.5 to 13.4 months) was greater than that of the GP method (precision, 8.45 %; LOA, −29.5 to 21.1 months).ConclusionsCH planimetry may be a reliable method for bone age assessment.Key Points• Bone age assessment is important in the work-up of paediatric endocrine disorders.• Radiography of the left hand is widely used to estimate bone age.• Capitatohamate planimetry is a reliable and reproducible method for assessing bone age.

Uniparental disomy as a cause of pediatric endocrine disorders.

.Uniparental disomy (UPD) refers to a condition in which two homologous chromosomes or chromosomal regions are inherited from one parent. Recent studies have shown that UPD is not rare among the general population, arising from trisomy rescue, gamete complementation, and other mechanisms. Although UPD is not necessarily pathogenic, it can lead to various disease phenotypes by causing imprinting disorders or by unmasking autosomal recessive mutations. Notably, known UPD-mediated autosomal recessive disorders include congenital adrenal hyperplasia due to 21-hydroxylase deficiency, 11β-hydroxylase deficiency, and 3β-hydroxysteroid dehydrogenase deficiency. In addition, UPD can occur in combination with additional cytogenetic abnormalities that may affect growth and development. Therefore, UPD represents a clinically important condition that accounts for a certain percentage of the etiology of growth failure and endocrine abnormalities. Although UPD is barely detectable by standard karyotyping or sequence analyses, it can be screened by single nucleotide polymorphism- and microsatellite-genotyping of patients and their parents, or by DNA methylation analysis of the patients. This mini-review introduces the underlying mechanisms and phenotypic consequences of UPD in association with pediatric endocrine disorders.

Three practical principles in planning and developing health care transition: our personal perspectives.

.Health care transition (HCT) is defined as an uninterrupted, coordinated, developmentally appropriate, psychosocially sound, and comprehensive process that is needed to assist the transition of young people from child to adult-centered care. Its importance has been discussed in pediatrics over the past decades but it is still a challenging subject to realize. In this mini-review, the authors present their personal opinions on HCT. The following are their three core suggestions: (1) patient-centered support and monitoring; (2) hospital-centered infrastructures with key personnel; and (3) flexibility in planning and modifying HCT procedures. We believe our recommendations could apply to most of the pediatric endocrine disorders, which usually require lifelong follow-up. This approach will be verified in the future.

Periodontal Disease and Dental Caries among children and Adolescents Suffering from Endocrine Disorders - A Literature Review.

Dental caries and periodontal disease are the most common oral diseases. Their link to disorders of endocrine system is of high interest. Most of the available data relates to the adult population, though its importance among children and adolescents is paramount. To review the existing evidence examining the link between these clinical conditions among children and adolescents. Electronic bibliographic databases and hand searches of relevant publications, based on prepared list of relevant key-words was performed. Paucity of existing data leaves the question of association between most endocrine disorders of the youth with dental caries and periodontal disease, inconclusive, apart from obesity and diabetes mellitus, where it seems to be elucidated. A profound research should be done in order to amend our understanding to what extent, if at all, exists the link between these oral maladies and different pediatric endocrine disorders.

PATTERN OF PAEDIATRIC ENDOCRINE DISORDERS AS SEEN AT A TERTIARY HEALTH FACILITY IN SOKOTO OVER A 4 -YEAR PERIOD

In most developing countries, data on the pattern of Paediatric Endocrine Disorders is lacking. To describe the pattern of Paediatric Endocrine Disorders as seen in Usmanu Danfodiyo University teaching Hospital (UDUTH), Sokoto, Nigeria, from January 2013 to December 2016. The case files of children seen at the paediatric endocrine/metabolic clinic and those admitted into the wards at UDUTH, Sokoto, from January 2013 to December 2016 were audited retrospectively. Information obtained included age at presentation, gender, principal complaints, final diagnosis and outcome. A total of 37 children presented with various endocrine disorders during the 4 - year- period under review. There were 20(54.1%) males, 15(40.5%) females, and 2(5.4%) patients with genital ambiguity. Patient's age ranged from 3weeks to 15years with a mean age and standard deviation (SD) of 6.9(5.2) years. Majority, 17(46%) of the patients were Adolescents. The endocrine disorders were thyroid disorders- 12(32.4%), diabetes Mellitus 9(24.3%), disorders of energy balance 4(10.8%), disorders of calcium and bone metabolism 4 (10.8%) and pubertal disorders 3(8.1%). Five (13.5%) patients were admitted, four were diabetics, three of which were discharged and 1(2.7%) died. Fifteen (40.5%) patients were lost to follow up in the endocrine clinic. Thyroid disorders, Diabetes Mellitus, Disorders of energy balance, Calcium and bone metabolism and pubertal disorders were the five leading groups of childhood endocrine disorders encountered in our clinical practice in UDUTH, Sokoto.

Pattern of Thyroid Disorders in Children and Adolescents Seen at the Lagos University Teaching Hospital, Nigeria, Over a 10-year Period.

Introduction:Thyroid disorders account for a large proportion of pediatric endocrine disorders. Untreated hypothyroidism in childhood has permanent adverse effects on physical, intellectual, and neurological development. However, few studies have reported the pattern of pediatric thyroid disorders in Nigeria.Objectives:The objective of this study was to document the pattern of thyroid disorders in children and adolescents seen at the Lagos University Teaching Hospital (LUTH) over a 10-year period.Participants and Methods:This is a retrospective descriptive study involving children with thyroid disorders seen from January 1, 2006 to December 31, 2015.Results:Seventy-one patients with thyroid disorders (0.13%) were seen out of 52,800 new cases (incidence of 1/1000 new cases) comprising 13.4% of 546 pediatric endocrine cases with a male:female ratio of 1:1.2. Median (range) age at presentation was 1.6 (0.001–14) years. Congenital hypothyroidism (CH) constituted a major proportion of cases (46.7%), with a median (range) age at presentation of 9 (1.5–24) months. Down syndrome constituted 45% of patients with CH with associated congenital heart defects in eight (53%) patients. Acquired hypothyroidism was seen in ten patients (five goitrous and five nongoitrous). Six patients had hypothyroidism associated with multiple anterior pituitary hormone deficiency. Nine patients (all females) had hyperthyroidism with confirmed Graves' disease in 5 (55.6%), with mean age at presentation being 9.4 ± 2.09 years. Other conditions were euthyroid sick syndrome (2.8%), euthyroid goiter (1.4%), and acute thyroiditis (1.4%). Eight infants of mothers on treatment for hyperthyroidism ( first seen between the 7th h of life to 2 months of age) had transient hypothyroidism while one 8-day-old had transient hyperthyroidism.Conclusion:CH was the most common disorder encountered with late age at presentation. Routine newborn screening and maintaining a high index of suspicion are advocated.

Next generation sequencing and array-based comparative genomic hybridization for molecular diagnosis of pediatric endocrine disorders.

Next-generation sequencing (NGS) and array-based comparative genomic hybridization (array CGH) have enabled us to perform high-throughput mutation screening and genome-wide copy number analysis, respectively. These methods can be used for molecular diagnosis of pediatric endocrine disorders. NGS has determined the frequency and phenotypic variation of mutations in several disease-associated genes. Furthermore, whole exome analysis using NGS has successfully identified several novel causative genes for endocrine disorders. Array CGH is currently used as the standard procedure for molecular cytogenetic analysis. Array CGH can detect various submicroscopic genomic rearrangements involving exons or enhancers of disease-associated genes. This review introduces some examples of the use of NGS and array CGH for the molecular diagnosis of pediatric endocrine disorders.

Association of environmental chemicals & estrogen metabolites in children

BackgroundThe prevalence of pediatric hormonal disorders and hormonally-sensitive cancers are rising. Chemicals including bisphenol A (BPA), phthalates, parabens, 4-nonylphenol (4NP) and triclosan have been linked to disruption of endocrine pathways and altered hormonal status in both animal and human studies. Additionally, changes in estrogen metabolism have been associated with pediatric endocrine disorders and linked to estrogen-dependent cancers. The main objective of the study was to measure the presence of these environmental chemicals in prepubescent children and assess the relationship between chemical metabolites and estrogen metabolism.Methods50 subjects (25 male, 25 female) were recruited from the principal investigator’s existing patient population at his pediatric primary care office. The first 5 boys and 5 girls in each age group (4 through 8 years old inclusive) who presented for annual examinations were included, as long as they were Tanner Stage I (prepubertal) on physical exam, without diagnosis of hormonally-related condition and/or cancer and able to give a urine sample. Urine samples were collected in glass containers for analysis of chemical and estrogen metabolites. Study kits and lab analysis were provided by Genova Diagnostics (Duluth, GA).Summary statistics for the concentrations of each chemical metabolite as well as estrogen metabolites were computed (minimum, maximum, median and inter-quartile range) for males only, for females only and for all subjects. Comparisons between groups (e.g. males v. females) were assessed using the nonparametric Wilcoxon test, since the data was skewed. The correlation between concentrations of chemical metabolites and estrogen metabolites in prepubescent children were examined by the Spearman’s correlation coefficient (ρ).Results100 % of subjects had detectable levels of at least one chemical in their urine, and 74 % had detectable levels of eight or more chemicals. 28 % of subjects had measurable levels of 4NP. No associations were found between the urine levels of chemicals and estrogen metabolites.ConclusionsEndocrine disrupting environmental chemicals were detected in all children in the study, with measurable levels of 4NP in nearly 1/3 of subjects. This is the first known published study of 4NP levels in American children. No associations were found between the urine levels of chemicals tested and estrogen metabolites. The presence of multiple chemicals in a majority of children’s urine coupled with increasing prevalence of pediatric hormonal disorders warrants further research to elucidate potential causal mechanisms in pre- and post-pubertal children.

Commentary: Launch of a Quality Improvement Network for Evidence-Based Management of Uncommon Pediatric Endocrine Disorders: Turner Syndrome as a Prototype

Traditional, hypothesis-oriented research approaches have thus far failed to generate sufficient evidence to achieve consensus about the management of children with many endocrine disorders, partly because of the rarity of these disorders and because of regulatory burdens unique to research in children. The Pediatric Endocrine Society is launching a quality improvement network in spring 2015 for the management of pediatric endocrine disorders that are relatively uncommon in any single practice and/or for which there is no consensus on management. The first of the quality improvement programs to be implemented seeks to improve the care of 11- to 17-year-old girls with Turner syndrome who require initiation of estrogen replacement therapy by providing a standardized clinical assessment and management plan (SCAMP) for transdermal estradiol treatment to induce pubertal development. The SCAMP algorithm represents a starting point within current best practice that is meant to undergo refinement through an iterative process of analysis of deidentified data collected in the course of clinical care by a network of pediatric endocrinologists. It is anticipated that this program will not only improve care, but will also result in actionable data that will generate new research hypotheses and changes in management of pediatric endocrine disorders.

Paediatric endocrine disorders as seen at the University of Benin Teaching Hospital over a ten-year period

Background : In most developing countries, data on the prevalence and distribution of paediatric endocrine disorders is lacking. Objective : To describe the pattern of endocrine disorders seen in the Department of Child Health, University of Benin Teaching Hospital (UBTH), Benin City, Nigeria between 2004 to 2013. Methods : In this retrospective study, the case files of children seen in the paediatric endocrinemetabolic clinic and those admitted into the wards at the UBTH, Benin City from January, 2004 to December, 2013 were audited. Information obtained included age at presentation, gender, principal complaints, and final diagnosis. For those who were admitted, the outcome was noted. The hospital’s paediatric clinic register was examined to obtain the total number of new cases seen during the period under review. Results : A total of 13,735 new cases were seen in the Department of Child Health, UBTH during the ten-year period under review and 99 (0.72%) of these had endocrine disorders. The frequencies of the four leading groups of endocrine disorders seen were as follows: diabetes mellitus 17.2%; disorders of sex development 13.8%; disorders of the thyroid gland 12.1%; and disorders of energy balance 11.2%. Short stature was a rare presenting complaint. Conclusion : Diabetes mellitus and disorders involving sex development, thyroid gland, energy balance and pubertal development were the five leading groups of childhood endocrine disorders encountered in our clinical practice in UBTH. Key words : endocrine disorders, clinical pattern, children, hospital, Nigeria.

New Paradigms in the Diagnosis and Management of Pediatric Endocrine Disorders

New Paradigms in the Diagnosis and Management of Pediatric Endocrine Disorders

Magnetic Resonance Imaging in Paediatric Psychoneuroendocrinology: A New Frontier for Understanding the Impact of Hormones on Emotion and Cognition

Mounting magnetic resonance imaging (MRI) research is characterising the neurobiological trajectories of healthy human brain development. In parallel, studies increasingly acknowledge the relevance of perturbations of these trajectories for adolescent and adult psychopathology. Although an influence of steroid hormones on mood and anxiety disorders has been demonstrated in adults, very little is known about how steroid hormones alter human brain development and contribute to adolescent psychopathology. This review focuses on recent evidence obtained from structural and functional MRI in children and adolescents with genetic endocrine disorders and with characteristic fluctuations in androgen or oestrogen levels (familial male precocious puberty, congenital adrenal hyperplasia, Klinefelter syndrome and Turner syndrome). It aims to highlight how neurobiological findings from these paediatric endocrine disorders can provide insight into the contribution of sex steroids with respect to the development of neurocircuitry involved in affective processing (amygdala, hippocampus) and cognitive control (prefrontal cortex, inferior frontal gyrus, striatum). In addition, findings from these populations may also provide important information on aberrant psychological processes relevant for the clinical care and management of these populations. Finally, the findings are discussed within the context of current frameworks in animal models, such as the organisational-activational hypothesis or the aromatisation hypothesis. The review ends with a discussion of open questions for future enquiry with the goal of integrating translational models with current knowledge of endocrine disorders and developmental studies in healthy populations.

Promoting Excellence in the Care of Pediatric Endocrine Diseases in the Developing World

On behalf of the Global Pediatric Endocrinology and Diabetes group, the authors provide a perspective on the rights of a child as enshrined in the United Nations Convention on the Rights of the Child (1989) concerning the care of pediatric endocrine disorders and diabetes mellitus, throughout the world, with particular reference to care in resource-constrained settings. In this article, we define the spectrum of health care needs of the child with an endocrine disorder and how they may be addressed, in terms of education, research, and development of sustainable programs for improved health outcomes. We emphasize the responsibilities of medical communities, the pharmaceutical industry, and relevant governments in promoting and supporting such concepts.

Transition of pediatric endocrine patients to adult care

The majority of children who are born with or who develop a chronic illness during childhood now survive into the adult years. This can present a considerable challenge to adult clinicians who might not be prepared to care for so-called pediatric disorders. This review presents concepts of transitioning for three pediatric endocrine disorders: Turner syndrome, congenital adrenal hyperplasia, and type I diabetes mellitus. Pediatricians have the responsibility of helping their pediatric patients learn to optimize their health, whereas adult clinicians must be willing to catch these older adolescents or young adults and help them deal with the challenges that their disorders present in addition to challenges complicated by adult living. A successful transition has considerable rewards for both patients and clinicians alike at both ends of the age spectrum.

Pediatric Endocrine Disorders of Energy Balance

The definition of obesity is a degree of somatic overweight that affords detrimental health consequences [1]. The majority of obesity in adulthood has its origins in childhood [2,3,4], making obesity a pediatric concern, and the prevention and treatment of obesity a pediatric goal. Weight gain obeys the First Rule of Thermodynamics, which states, “The total energy of the system plus the surroundings is constant”. Energy can neither be created nor destroyed, but can be transformed to matter and vice-versa. In human terms, “calories in = calories out + weight gain”. Obesity, in the simplest statement of pathophysiology, is a dysregulation of either increased energy intake or decreased energy expenditure or both to favor excessive weight gain [5]. Many lay “experts” consider obesity to be an aberrant behavior; the pathophysiologic result of gluttony and sloth. Within the scientific community, the discovery of leptin and the elucidation of various monogenic disorders of obesity and genetic linkages, has promulgated the notion that obesity is a disease. Instead, it is more correct to consider obesity as a phenotype of many different pathologic processes, which impact at various points on the negative feedback pathway of energy balance. Various processes can promote an obligate and primary weight gain, and that increased energy intake and decreased energy expenditure may secondarily result. Many of the defects in the negative feedback energy balance pathway result in an increased storage of energy in adipose tissue due to increased lipogenesis, decreased lipolysis, or both. This review will elucidate the genetic/endocrine disorders that promote weight gain and obesity in children.

Paediatric Endocrine Disorders

This is an excellent book on Paediatric Endocrine disorders published in India for the first time, It has contributions from National and International authors. Endocrine disorders are not very common in children and adolescents but they should be diagnosed early and treated appropriately to prevent long term effects in a growing child. This is a comprehensive book giving clear guidelines for paediatricians on when to suspect an endocrine problem, laboratory tests to be performed and reference to paediatric endocrinologist. The topics of growth, puberty, sexual differentiation, diabetes. thyroid, adrenals etc have been well covered. However, there are a few drawbacks in the book. There should have been an introductory chapter with a general discussion on clinical features in endocrine disorders. There are too many abbreviations in the text and some tables have numerous arrows and long legends. Despite all these drawbacks this book is strongly recommended for all postgraduate students and paediatricians.