Practical Pediatric Endocrinology in a Limited Resource Setting

Practical Pediatric Endocrinology in a Limited Resource Setting provides a guide for managing pediatric endocrine problems in a limited resource setting, together with an outline of the bases for these disorders. The book outlines a plan for coming to a likely diagnosis in situations where resources are constrained, and suggests ways to access more sophisticated technologies for diagnostic confirmation and extension of available tools.

Further extending and complementing each chapter is a series of scenarios for use as teaching and learning tools. Together with a clinical question, all chapters include a suggested outline for assessment that assists readers facing similar situations in daily practice. Each scenario works through a typical series of deductive steps used to establish a working diagnosis, while considering both a differential diagnosis and reminding readers of current knowledge around the subject matter.

• Provides a working knowledge of pediatric endocrinology, from the viewpoint of practical application, for residents and clinicians practicing in settings with scarce material resources
• Features clinically based chapters, empahsising workable diagnoses and management plans in limited resource situations
• Includes information on Type 1 diabetes mellitus, given its increasing prevalence worldwide
• Describes basic research techniques and planning, intended to foster collaboration between colleagues and other centers in clinical or basic research, which can inform clinical practice and drive innovation

• Language: English
• Publisher: Academic Press
• Release date: Apr 11, 2013
• ISBN: 9780124079366

Book preview

Vancouver

Preface

Although pediatric endocrinology is a relatively new speciality, the pace of change has been rapid over the past 10 – 20 years. Technological advances and electronic communications have totally changed not only the face of medicine in westernized countries but also the ability to reach, recognise, diagnose and treat health problems in the developing world. Along with medical advances, major changes in education and travel have enabled patients to seek advice from major centres and medical staff to access information and specialist training. Formation of new special interest groups and societies with international exchanges provide new options for the future.

Visiting and teaching in several developing countries over recent years, my colleagues and I have been enormously and consistently impressed by the level of knowledge, and dedication achieved under very often difficult circumstances, in resource constrained environments. An outstanding need appeared to be provision of practical guidelines for assessment and treatment of pediatric endocrine conditions for those working in these areas.

This book was conceived as an accessible and useful resource for pediatricians and other health care workers, aiming to provide clear diagnostic outlines and management strategies. Many experienced endocrinologists around the world have contributed to this book, several of whom have travelled and taught widely in the developing world. The resulting book was not intended to take the place of standard texts. It is intended to provide brief, up to date background information for endocrine conditions with an emphasis on diagnostic possibilities, practical low cost investigations and treatment where indicated. A guide as to how to access more sophisticated technologies where needed, is also provided.

Development of a broader knowledge base in medicine requires an ability to access and interpret medical literature. For this reason we have included a short chapter to serve as an introduction to basic molecular biology, so that the reader may better understand, interpret and assimilate an increasingly vast amount of complex information.

We have also included a chapter concerning research. Particularly in the developing world there has been a relative lack of knowledge concerning prevalence and incidence of many endocrine conditions, limited in part by distance, financial constraint and patient education to seek advice. We emphasise the importance of simple research protocols to help recognise these vital issues. Such research will inform local practice and in turn will provide a basis for accessing government support for future funding and preventative care. We hope that undertaking research and providing innovative care will also sustain practitioner interest.

In many places newly trained Pediatric Endocrinologists are returning to their own countries, as perhaps one of the first to practice in the speciality. Although knowledge may be thorough, clinical judgment takes time and experience. For this reason, we have provided a section with typical endocrine scenarios, worked through by different authors, to complement the clinical chapters and to extend and assist with development of this important aspect of medicine, whilst being mindful of possible burdens imposed upon families by possibly excessive expenditure on non- essential investigations.

Two of the most important emerging worldwide endocrine issues are obesity and both type 1 and type 2 diabetes mellitus. Particularly in the developing world with better living conditions and access to improved nutrition, both problems are increasing at a rate similar to that in westernized countries. I am grateful to Professor Stuart Brink for providing a brief version of his recently published book "Basic Training for Healthcare Professionals in Developing Countries". My thanks also go to Drs Justin Brown, Michele O’Connell and Professor Garry Warne for providing scenarios and helpful suggestions to improve chapters.

Other resources available complement this volume include an e-learning program accessible through the European Society of Paediatric Endocrinology at http://www.sb-elearning.org, and a Colour Atlas of Paediatric Endocrinology and Growth by Wales J, Rogol A, and Witt J, that can be accessed through Amazon.com.

We hope we have succeeded in filling a gap, to provide working knowledge and practical application towards pediatric endocrinological diagnosis and management, for pediatricians in circumstances where material resources may be limited and where the need to provide accurate and acceptable care to families is paramount.

Margaret Zacharin

Melbourne, December 2012

Chapter 1

Growth

Importance and Implications of Variations

Jaya Sujatha Gopal-Kothandapani, Indraneel Banerjee and Leena Patel

Outline

Part 1: Normal Growth and Puberty

Part 2: Variations in Linear Growth

Specific Conditions Presenting with Short Stature and Growth Failure

Tall Stature

Specific Conditions Presenting with Tall Stature

References and Further Reading

Part 1: Normal Growth and Puberty

Introduction

Growth is a complex dynamic process by which the body and various structures within the body increase in size. Normal growth results from the careful co-ordination of three cellular processes: (1) an increase in the number of cells or cell hyperplasia, (2) increase in the size of cells or cell hypertrophy and (3) programmed cell death or apoptosis. It involves tissues, organs, body parts and the whole body, and any or all of these can be affected when growth is disrupted. Although the term ’growth’ has a wide definition, we have restricted its use to growth in height or linear growth for the purpose of this chapter. The growth pattern of a child and adolescent is a good indicator of:

• health and general well-being

• nutritional status

• disease activity and response to treatment of any underlying illness.

Commonly Used Terms

Interpreting growth measurements for any individual child requires comparing with reference values. The reference can be the child’s previous measurements and/or those derived from measurements of a sample of healthy children in a population. For example, a child’s height at a particular age can be compared with the child’s height measurements at previous time points, if available, as well as with a height reference such as the WHO Child Growth Standards. The height reference may be available as a table or as a growth chart.

A histogram of height measurements from a reference sample shows a bell-shaped or Gaussian distribution, also conventionally described as a ’normal’ distribution (Figure 1.1). This is because a greater proportion of the measurements will cluster around the average and the number of measurements that are further away from the average are fewer. The mean is the average value for a bell-shaped distribution and standard deviation describes the spread of values. Percentiles, or centiles, represent the percentage of the population that falls below that point. Thus in a bell-shaped distribution the mean represents the 50th centile and this simply indicates that 50% of the values will fall below while 50% will be above the mean. The 3rd, 15th, 50th, 85th and 97th centiles are shown in the WHO growth charts (Figure 1.2).

FIGURE 1.1 ’Normal’, bell-shaped or Gaussian distribution from smoothed out histogram of height measurements from a reference population sample.

FIGURE 1.2 Length/height distance chart showing 3rd, 15th, 50th, 85th and 97th centile lines for the reference population.

A ’normal’ curve with a mean of 0 and a standard deviation of 1 is called a standard normal curve (Figure 1.2; Table 1.1). The Empirical Rule can be applied to this, such that approximately:

• 68% of the values will fall within 1 standard deviation of the mean in either direction

• 95% of the values will fall within 2 standard deviations of the mean in either direction

• 99.7% of the values fall within 3 standard deviations of the mean in either direction.

TABLE 1.1

Approximate Relationships Between Percentiles and Standard Deviations for a Standard Normal Distribution

Since only 5% of measurements from healthy children fall outside the range between –2 and +2 standard deviations, a height below or above this range is more likely to be abnormal than normal. In the absence of a defined cut-off for abnormal growth measurements, the probability of whether a measurement is likely to be normal or abnormal is useful in clinical practice.

Any ’normal’ distribution can be standardised by converting the mean to zero and the standard deviation to one. For a measured value (e.g. height), the standard deviation score (SDS) or z-score can be calculated (measured value minus mean value/standard deviation), and then the corresponding percentile can be obtained from probability tables (found in textbooks on statistics). Converting observed growth measurements into SDS is useful in clinical research and allows comparisons to be made irrespective of age, gender and ethnic background.

Types of Growth Charts

Gender specific height, weight and head circumference centile charts are widely used in clinical practice. They represent age on the horizontal axis and include selected centiles for reference populations from different countries (Figure 1.2 shows the WHO length/height-for-age chart for girls). These are described as distance charts. The centile lines on a distance chart show the normal pattern of growth through childhood and adolescence. Charts for other growth measurements (such as sitting height and subischial leg length) and disease-specific growth charts (e.g. Turner syndrome, Down syndrome) are also available. Growth velocity charts illustrate the rate of change in measurements per year on the vertical axis and age on the horizontal axis (Figure 1.3). However, they may not be available for different populations worldwide.

FIGURE 1.3 Height velocity chart showing the 50th centile for girls (light grey) and boys (dark grey).

Problems can arise with use of a growth chart derived from different population data. Previously, WHO data were derived from the National Centre for Health Statistics (NCHS) standards from North America. The most recent WHO growth charts are derived from longitudinal growth data in optimally nourished children from six different countries, including those that are relatively underdeveloped. While these charts are not necessarily representative of undernourished children in developing countries, they aim to provide a common international reference standard, which may be adopted for use in countries where recent national standards are not available. If possible, the development of a local national standard should be encouraged. These standards should be updated over time to take into account secular trends and shifting economic and nutritional status in those countries.

Phases of Linear Growth

Normal growth is a continuous process with a predictable pattern. It starts prenatally and continues until the epiphyses at the ends of long bones are fused. The latter occurs when full pubertal maturation is achieved. Deviations from the normal pattern of growth provide clues to the state of health of a child and possible underlying pathology.

The period of growth can be subdivided into a phase before birth and three phases after birth:

1 Fetal phase: During this phase a single fertilised egg grows and develops over 9 months into an infant with an average length of about 50 cm. Thus the growth rate or height velocity during this phase is the fastest (approximately 70 cm/year).

2 Infancy phase: Although considerable growth occurs initially and length increases by about 23–25 cm in the first year, the rate of growth rapidly declines to about 9 cm/year by age 2 years and 7 cm/year by age 4 years.

3 Childhood phase: Through mid-childhood from age 4 years and until the onset of puberty, growth velocity remains relatively steady at around 5–7 cm/year.

4 Puberty phase: This phase begins with the onset of puberty and ends when adult height is attained. It is characterised by the development of secondary sex characteristics and a pubertal growth spurt when the peak growth rate increases dramatically to an average of 8 cm/year in girls and 10 cm/year in boys. The timing of the onset of puberty, peak growth rate and cessation of growth occurs earlier in girls compared to boys, and contributes to men being nearly 12.5 cm taller than women.

Key Factors which Regulate Growth and Basic Requirements for Normal Growth

Genes, nutrition and hormones have important effects on fetal and postnatal growth. Fetal growth is determined by the availability of glucose in utero and influenced by the IGF system. Nutrition, insulin and IGF-I regulate growth in early infancy and growth hormone begins to have an effect from the second 6 months of life. During puberty, growth is regulated by both growth hormone and sex steroids. Other hormones necessary for normal growth but which do not directly control growth are:

• thyroid hormones

• vitamin D

• insulin

• leptin

• glucocorticoids.

In addition to these factors, there are some basic requirements for normal growth and without them growth is adversely affected (Table 1.2).

TABLE 1.2

Basic Requirements for Normal Growth and Examples of Conditions When these are not Available and Growth is Adversely Affected

Clinical Assessment of Growth

Clinical assessment of growth requires thorough:

• history

• growth measurements

• pubertal staging

• clinical examination.

History

A history from the child who is able to communicate and carers provides valuable information about their specific concerns, beliefs and expectations. The key components are presented in Table 1.3.

TABLE 1.3

Key Components of the History for the Assessment of Growth

• Presenting complaint: short or tall; early, delayed or arrested puberty; associated symptoms such as weight loss or weight gain.

• Duration of the problem and progress.

• Past history: symptoms associated with specific syndromes, hypothalamic-pituitary lesions, systemic illness.

• Dietetic history: estimated food energy and protein intake, history suggestive of vitamin or mineral deficiency, missed meals, lean periods, diarrhoea, vomiting, skin changes suggestive of malnutrition.

• Medications: prolonged corticosteroid treatment.

• Antenatal details: maternal health, illness, medications, alcohol, recreational drugs.

• Fetal monitoring history: ultrasound scan, fetal movements.

• Birth details: gestation at birth, mode of delivery, need for resuscitation, birth weight, length, head circumference.

• Postnatal period: hypoglycaemia, jaundice, feeding difficulties, floppiness, surgery in the neonatal period, unusual features such as puffy feet, hands and neck.

• Neurodevelopment: problems with speech, hearing, learning, vision, behaviour.

• Family history: consanguinity, mother’s and father’s height, mother’s and sister’s age at menarche, father’s and brother’s age at pubertal growth spurt and starting to shave, family members with growth disorders, known inherited or auto-immune conditions.

• Social background: parents’ education, employment, income, stress in family.

• School and social activities: academic performance, behaviour, friends; physical and/or psychological impact such as bullying and emotional problems.

Growth Measurements: Anthropometry

For any growth measurement, repeated measurements over time are more informative than single measurements as they show the pattern of growth and growth velocity.

Weight

Infants should be weighed naked and children with minimal clothing using accurately calibrated scales. Weight should be recorded in kilograms and to the nearest 100 grams.

A number of formulae are available for estimating average weight for a healthy child by age (Table 1.4). The weight derived from these formulae is only a rough guide to the estimated weight. It is advisable to weigh accurately and to plot on reference standards, such as the WHO centiles.

TABLE 1.4

Formulae for Estimating Average Weight and Standing Height

Supine length and standing height

Supine length should be measured from birth to 2 years and older children who are unable to stand independently. Standing height is measured in children older than age 2 years who can stand independently. The instruments available for measuring length range from simple, relatively cheap boards, light portable measuring mats which can be rolled up to more sophisticated equipment such as the Harpenden neonatometer. For standing height, fixed wall-mounted stadiometers as well as portable equipment can be used (such as Minimetre and the Leicester Height Metre). The range of error is greater with wall charts compared to a stadiometer. It must be appreciated that even stadiometers may be susceptible to error. Error can arise from:

• inappropriate installation of equipment, positioned incorrectly

• incorrect use, such as faulty setting of the digital counter of a stadiometer owing to rough handling

• incorrect technique of positioning the child

• unco-operative child.

A solid rod of known length should be used to calibrate the equipment. The most important aspect of measuring length and height is the technique of positioning the child. This remains uniform irrespective of the equipment used (Figure 1.4). Although height can be measured by one person, length requires two people.

FIGURE 1.4 Techniques for measuring (A) supine length and (B) standing height.

The measurements should be recorded in centimetres and to the nearest millimetre. Whenever possible, serial measurements should be made with the interval between measurements at least 3 months or more.

Interpreting length and height measurements

A child’s growth measurements should be plotted on centile charts so that comparisons can be made with the reference population. In addition, the child’s height needs to be interpreted in the context of parents’ heights (Figure 1.5). When possible, parents’ heights should be obtained by direct measurement rather than relying on reported values, which are likely to be error prone. Midparental height is an indicator of the child’s growth potential based on the genetic background. Midparental height is calculated as:

FIGURE 1.5 Height distance chart for boys.

Note: The reference centile lines as well as parents’ heights are useful for interpreting the growth of a child. A growth trajectory that is parallel to the reference centiles indicates normal height velocity. Deviation downwards suggests poor linear growth (A), and upwards suggests rapid growth (B). The initial height of child A and child B would be considered appropriate for father 1 (F1) and mother 1 (M1) but short for parents F2 and