Continuing professional development
Educating children and families about growth hormone deficiency and its management: part 1 NCYP699 Collin J et al (2016) Educating children and families about growth hormone deficiency and its management: part 1. Nursing Children and Young People. 28, 1, 32-36. Date of submission: September 12 2015. Date of acceptance: November 17 2015. Correspondence [email protected]
Abstract The management of growth hormone deficiency is long term. Children may be diagnosed at pre-school age meaning relationships with the paediatric endocrine team may last more than 15 years. The education role of the paediatric endocrine nurse specialist is essential in working in partnership with families over a long period of time. Children and young people have changing needs for information to help them understand their condition and growth hormone deficiency treatment as they grow up. Developing positive working relationships with parents, children and young people enables their developmental needs and the context in which they live their lives to be central to any educational planning for them. Addressing developmental needs when providing information on growth hormone deficiency to children and young people reinforces the need for education to be an ongoing process and not a one-off event. This is part one of a two-part article. The second part will be published in the March issue of Nursing Children and Young People and it focuses on educating children, young people and their parents about the condition, and includes case studies.
Aims and intended learning outcomes The aim of this article is to examine how paediatric endocrine nurse specialists (PENS) meet the educational needs of children and young people and their parents following a diagnosis of growth hormone deficiency (GHD). This article will enable you to: ■ Review the function of growth hormone (GH). ■ Obtain an overview of the causes of GHD and clinical presentations. ■ Understand conditions where growth hormone therapy (GHT) is recommended. ■ Develop insight into the development of GHT. ■ Gain an overview of the importance of building partnerships with parents. GHD is the most common endocrine condition presenting in children with short stature, occurring in approximately one in 3,500-4,000 (National Institute for Health and Care Excellence (NICE) 2010, Raine et al 2011). Physiological replacement of GH is the treatment for this condition. Following diagnosis 32 February 2016 | Volume 28 | Number 1
children commence a daily subcutaneous injection/ transjection of synthetic recombinant human growth hormone (rHGH). GH replacement is necessary for these children to reach their target for final adult height (Martin and Collin 2015). Treatment continues for many years, often into adulthood. Successful outcomes for children, young people and their parents largely depend on a clear understanding of the condition and its long-term management. Educating and supporting children, young people and their families is an essential role of the PENS. Partnership working is key to enabling children and their families to manage the impact of this long-term treatment on their day-to-day lives, and promoting adherence with the management plan.
Jacqueline Collin is lecturer/ head of department, child and adolescent nursing, King’s College London Amanda Whitehead and Jenny Walker are children’s endocrine specialist nurses, Leeds Teaching Hospitals NHS Trust Keywords Child health, children development, endocrine nurse specialist, growth hormone deficiency, growth hormone therapy, paediatrics, parents Conflict of interest None declared Peer review This article has been subject to open peer review and checked using antiplagiarism software. For related articles visit our online archive and search using the keywords Author guidelines journals.rcni.com/r/ ncyp-author-guidelines
Role of growth hormone
GH is the main regulator of human growth ensuring all parts of the body, including organs, grow in proportion (Raine et al 2011). Nutrition has a dominant role in intrauterine growth, which means that infants with NURSING CHILDREN AND YOUNG PEOPLE
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idiopathic GHD are rarely identified at birth; however, from about two years of age the hypothalamic-pituitary axis becomes increasingly important with GH taking up its primary role in stimulating childhood growth and maintenance of tissues throughout the body (Raine et al 2011, Kirk 2012). The anterior pituitary gland synthesises and secretes GH. The process is regulated by neurosecretory nuclei of the hypothalamus (Raine et al 2011). These cells release peptides called growth hormone releasing hormone and somatostatin into the hypophyseal portal venous blood supply which surrounds the pituitary. GH release is pulsatile in nature, determined by a balance between these stimulating and inhibitory peptides. Additional influence comes from other physiological stimulators such as exercise and sleep or from inhibitors such as free fatty acids (Raine et al 2011). GH can be seen to affect growth directly, and most obviously, by acting on epiphyseal growth plates to produce linear growth, but it also acts indirectly by the production of growth factors (Laycock and Meeran 2013). In the liver GH stimulates production of a protein called insulin-like growth factor (IGF-1), which is the main mediator of many of the actions of GH. IGF-1 is responsible for promoting growth in the post-natal period. It stimulates cell division, thereby influencing cartilage cells at the end of long bones to multiply, which in turn lengthens the bone (Laing 2014). IGF-1 is the main GH-dependent growth factor and its measurement correlates well with spontaneous GH secretion and for this reason it is used in the diagnosis of GHD. Early identification of poor growth is important because GH has a profound effect on growth during the early years of life and will affect a child’s final adult height (Figure 1). Insufficient amounts of GH means children’s growth may be poor resulting in short stature (Laycock and Meeran 2013). As children reach puberty, the pubertal growth spurt is triggered by an increase in concentrations of GH in conjunction with sex hormones and insufficiency in these hormones will significantly affect the child’s final height. Puberty heralds the end of linear growth; consequently treatment has to be optimised before puberty. After puberty cartilage is converted to bone, meaning that IGF-1 will have little or no effect in further increasing bone length. GH stimulates growth and maintains general tissues in the body; however, not all of its functions are completely understood yet (Laycock and Meeran 2013). The process of growth is complex and involves the synthesis of molecules in all tissues of the body; hence, the influence of GH in the regulation of metabolism of proteins, lipids and carbohydrates throughout life (NICE 2010). NURSING CHILDREN AND YOUNG PEOPLE
Figure 1 Measuring children is important to assess the effects of growth hormone
Causes of growth hormone deficiency
Common causes of GHD are congenital, acquired or idiopathic (Kirk 2012). The vast majority of children diagnosed with GHD have no identifiable cause. This is described as isolated idiopathic GHD and accounts for 50-70% of patients (NICE 2010, Kirk 2012). More boys present with GHD than girls, although the reason for this is not known. GHD is not always isolated and can be associated with other anterior and posterior pituitary hormone deficiencies arising from hypopituitarism (Raine et al 2011); for example, thyroid stimulating hormone may be affected or adrenocorticotropic hormone. There are familial forms of GHD: autosomal recessive, autosomal dominant or X-linked recessive, which determine the severity of the condition. Children can also develop acquired GHD which may occur as a result of injury, infection or tumour growth in the hypothalamic pituitary region such as craniopharyngiomas (Dattani and Preece 2004). Treatment of tumour growth by surgery or cranial irradiation may cause some damage to the pituitary gland which then fails to function adequately putting children at risk of GHD. The terms GHD or insufficiency are often used interchangeably, however, they are different and reflect the nature of the child’s problem – deficiency relates to very low levels whereas insufficiency refers to inadequate GH production. Other reasons for growth failure in children are identified in Box 1. February 2016 | Volume 28 | Number 1 33
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Continuing professional development Box 1 Conditions where growth hormone therapy is recommended ■ Growth hormone deficiency ■ Turner syndrome ■ Prader-Willi syndrome. ■ Growth failure at four years or older and born small for gestational age ■ Short stature homeobox – containing gene (SHOX) deficiency. ■ Chronic renal insufficiency.
Not all children present in exactly the same way because this will depend on the cause of their GHD (Kirk 2012). Invasive investigations to confirm a diagnosis of GHD are undertaken when all other possibilities have been excluded. Initial investigations commonly undertaken are summarised in Box 2. Growth hormone has a peak concentration during a child’s sleep and, therefore, the treatment using GH replacement works most effectively when administered once a day in the evening. Now do time out 1
Not all children and young people who are short have a GHD. Healthy children whose family is shorter than average may have a height appropriate for their genetic background. Other children may be referred because they are shorter and their sexual maturation is delayed. This is described as constitutional delay. Typically they will reach their adult height albeit later than their peers. Treatment with GH for these children is an area of professional and ethical debate (Morrison 2015). Referral to specialist endocrine services is usually triggered by concerns of parents or community health practitioners in relation to short stature, absent or very low rate of growth (Martin and Collin 2015). GH binds to adipocytes and causes them to break down triglycerides affecting fat storage in the body, hence children with GHD tend to have a greater weight to height ratio and may appear overweight. Slow growth may be noticed during infancy, but is more commonly noticed from the age of two years, although a referral may occur at any time during childhood. Commonly parents become aware that their child is in younger clothes sizes and is significantly smaller than their peers. An unexpected growth pattern is recognised in the sequential measurements recorded since birth and healthcare professionals trigger referral for investigation. Although very short, children with GHD have normal body proportions and parents can be reassured that the child’s intellect is unaffected. Physical development is delayed and children may look younger than they are as their skeletal maturity/bone age is delayed; for example, immature growth of the skull means the child will have facial proportions of a younger child described as midfacial hypoplasia, small hands and feet and hypoglycaemia may occur in neonates (Kirk 2012). Children may be treated and spoken to as though they are younger than their chronological age. Erling (2004) describes ‘juvenilisation’ as a risk factor for the emotional and social development of children with short stature because of lower expectations by adults of their abilities, isolation by their peers and limited opportunities to develop independent living skills, which potentially erodes their confidence and sense of autonomy. 34 February 2016 | Volume 28 | Number 1
1
Warning signs
Time out
(National Institute for Health and Care Excellence 2010)
Describe the concerns and cues that would alert parents and healthcare professionals to refer a child to specialist endocrine services?
Growth hormone therapy
Replacement therapy has not always been as straightforward as it is now. Tattersall (1996) reports that the importance of the pituitary gland in relation to growth was first identified in 1886 when Pierre Marie (1853-1940) reviewed reported cases of acromegaly and made a connection with pituitary tumours. Further experiments throughout the 1920s and 1930s added weight to these early findings and, by the 1940s, bovine and porcine GH was successfully isolated. However, this was not useful in the treatment of GHD in children because it became clear that GH was species specific (Tattersall 1996); only human growth hormone (HGH) from human pituitaries could produce growth in children (Morrison 2015). The supply of HGH was limited as Box 2 Initial investigations ■ Review of previous weight and height on standardised growth charts ■ Target centile range using parental heights ■ Calculation of growth rate ■ Bone age of left hand and wrist ■ Magnetic resonance imaging of the head ■ Baseline blood testing ■ Pituitary testing consisting of stimulation tests which are designed to stimulate the production of GH. NICE guidelines state that a diagnosis of GHD requires two GH provocation (stimulation) tests to be performed. The diagnostic testing involved is discussed in detail in the third article in this series, which explains clinical investigations (National Institute for Health and Care Excellence 2010, Davies and Collin 2015)
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NURSING CHILDREN AND YOUNG PEOPLE
Table 1 Supply of recombinant human growth hormone (somatropin) Company
Growth hormone
Device/s
Pfizer
Genotropin
Genotropin pen/ Genotropin miniquick
Novo Nordisk
Norditropin simpleXx
Nordipen/ Nordiflex
Merck Serono
Saizen
Easypod
Ferring
Zomacton
Zomajet
Sandoz
Omnitrope
Surepal
Ipsen
NutropinAq
NutropinAq pen
Eli Lilly
Humatrope
Humatropen
GH and states, for example: ‘The dosage varies according to the condition being treated: 23-39 microgram/kg daily or 0.7–1.0 mg/m2 daily for GHD’. The growth response of the products from the different companies is the same; however, differences exist in the injection devices and support services offered. These differences contribute to decisions families make about devices they ultimately choose. The majority of centres offer an open choice of device, although there may be local differences that would be clarified by the PENS. Most GH in the UK is prescribed on a shared care basis between primary, secondary and tertiary care, with GPs taking responsibility for prescribing and the lead centre taking responsibility for the initial diagnosis, monitoring and adjustment of therapy (Kirk 2012). PENS liaise to facilitate communication between specialist and primary health care services to ensure any changes to GHT are seamless for families (Jones 2014). Now do time out 2
2
True or false?
Time out
it could only become available from pituitary glands from cadavers (Tattersall 1996). In 1956 American biochemists first isolated HGH from human pituitary glands and in 1958 its first clinical use successfully illustrating increased growth rate and height in childhood GHD was reported (Kirk 2012). Regulatory bodies were set up – the National Pituitary Agency in the United States and the Medical Research Council in the United Kingdom. A pituitary hormone committee was organised to develop clinical trials to examine the potential of HGH as a treatment for children with extreme short stature (Morrison 2015). Limited availability of HGH meant that only children with severe short stature were treated. Two important events occurred in 1985 that would change this situation. The first was withdrawal of HGH following reported cases of a fatal neurological disease – Creutzfeldt-Jakob disease – diagnosed in patients who had been treated from the 1960s. Potentially many people could be infected from one batch of GH, which was formed from up to 2,000 human pituitary glands, pooled and divided into individual doses for distribution. Later that year a biosynthetic version of GH – rHGH – became available for clinical use. Recombinant technology involves the insertion of genes into cells that solved the problem of disease transmission and addressed the limited supply (Kirk 2012, Morrison 2015). Until this point only the most severely affected children were treated, but since 1985 all children with inadequate levels of GH have had an opportunity to receive replacement therapy. However, parents may not always have the same view as their children about GHD and GHT, which may affect adherence in the long term (Upton et al 2008). Research with children aged more than ten years, focusing on the implications of parent and child quality of life assessments underpinning decisions about GHT, identified that many clinical decisions are based on the presumption of ‘future benefits rather than current disadvantages’ (Otero et al 2103). The advice from NICE (2010) is children’s views about GHT and their perceptions about their short stature need to be discussed with them to inform the treatment decision. Children with severe GHD who are left untreated can have a final height of 130-140cm (Kirk 2012). The main purpose of treatment is to normalise growth. GH is licensed by NICE to treat specific childhood conditions identified in Box 1. Several pharmaceutical companies are involved in the development and production of rHGH. Each product is produced by recombinant DNA technology and has a sequence identical to HGH (NICE 2010). There are currently seven preparations of somatropin available in the UK, listed in Table 1. Treatment is individualised to meet the requirement of each child. NICE (2010) provides guidance for the use of
Which of the following statements are true or false? 1. Human growth hormone is species specific. 2. Recombinant technology involves insertion of genes into cells and prevents transmission of disease. 3. The primary aim of growth hormone therapy is to improve bone density. 4. In the UK the licence for growth hormone means children diagnosed with growth hormone deficiency, Turner syndrome and chronic renal insufficiency are eligible for growth hormone therapy. 5. The growth response of different products varies.
February 2016 | Volume 28 | Number 1 35
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Continuing professional development The long-term nature of GHT means that parents experience a burden of care that poses challenges at different ages and stages of their child’s development (Kremidas et al 2013, Otero et al 2013). The primary aim for PENS is to develop a therapeutic relationship with parents from the outset. The timing of the first meeting with families will vary. For some it may be within the investigative period, for others it may be when the diagnosis is confirmed, or later, at a home visit to teach families about GHD and commence treatment. However, the primary aim remains: to establish a therapeutic relationship leading to partnership working, enabling families to be empowered and self-assured in balancing their child’s medical and developmental needs. In Western culture being tall is perceived as a positive characteristic, whereas being short is seen as less desirable. Social stereotypes related to height are established at an early age and are considered to result in social stigma (Voss and Sandberg 2004). However, although short stature does not always result in negative psychosocial experiences for children and young people (Erling 2004, Otero et al 2013), it is an anxiety frequently expressed by parents. To develop a helping relationship with parents, an empathetic approach is needed by the PENS. Individual concerns can be addressed, while maintaining an objective approach to planning, teaching and supporting care at home. Information sharing and education is central to collaborative working with parents, enabling them to develop their expertise in parenting their children with GHD. Commencing GHT is a pivotal point in the development of relationships lasting many years between children, parents, the endocrine team and the PENS. Part 2 explores the role of PENS in educating families in relation to the management of GHT.
Conclusion
The medical management of GHD in children and young people significantly changed once GH replacement therapy became widely available in 1985. GHD is a long-term condition and the PENS is pivotal to education and support of families. When normalising growth through GHT, successful outcome is gradual, and children and young people subjected to daily injections may find this frustrating. The skill of the PENS lies in maintaining the engagement of parents, children and young people over many years, to promote a successful treatment outcome that makes the years of physical, emotional and social investment in their growth worthwhile. Now do time out 3
3 Time out
Partnerships with parents
Reflective account Now that you have completed this article you may want to complete the questionnaire on page 37 and write a reflective account of between 750-1,000 words. Go to journals.rcni.com/r/ ncyp-reflective-account to find out more. If you are an online subscriber, you can place these in your portfolio.
Answers to time out 2 1. True, 2. True, 3. False, 4. True, 5. False
Online archive For related information, visit our online archive and search using the keywords
References Dattani M, Preece M (2004) Growth hormone deficiency and related disorders: insights into causation, diagnosis, and treatment. The Lancet. 363, 9425, 1977-1987. Davies K, Collin J (2015) Understanding clinical investigations in children’s endocrinology. Nursing Children and Young People. 27, 8, 26-36. Erling A (2004) Why do some children of short stature develop psychologically well while others have problems? European Journal of Endocrinology. 151, Suppl 1, S35-S39. Jones J (2014) A strong relationship for a long journey. British Journal of Nursing. 23, Suppl 6, S10-S11.
Kirk J (2012) Indications for growth hormone therapy in children. Archives of Disease in Childhood. 97, 1, 63-68. Kremidas D et al (2013) Administration burden associated with recombinant human growth hormone treatment: perspectives of patients and caregivers. Journal of Pediatric Nursing. 28, 1, 55-63. Laing P (2014) Growth failure and hormone therapy. British Journal of Nursing. 23, Suppl 6, S3-S9. Laycock J, Meeran K (2013) Integrated Endocrinology. Wiley-Blackwell, Chichester. Martin L, Collin J (2015) An introduction to growth and atypical growth in childhood and adolescence. Nursing Children and Young People. 27, 6, 29-37.
36 February 2016 | Volume 28 | Number 1
Morrison M (2015) Growth hormone, enhancement and the pharmaceuticalisation of short stature. Social Science and Medicine. 131, 305-312. National Institute for Health and Care Excellence (2010) Human Growth Hormone (Somatropin) for the Treatment of Growth Failure in Children: Technology Appraisal Guidance TA188. NICE, London. Otero SC et al (2013) Implications of parent and child quality of life assessments for decisions about growth hormone treatment in eligible children. Child: Care, Health and Development. 39, 6, 782-788.
Tattersall R (1996) A history of growth hormone. Hormone Research. 46, 4-5, 236-247. Upton P et al (2008) Parent-child agreement across child health-related quality of life instruments: a review of the literature. Quality of Life Research. 17, 6, 895-913. Voss LD, Sandberg DE (2004) The psychological burden of short stature: evidence against. European Journal of Endocrinology. 151, Suppl 1, S29-S33.
Raine JE et al (2011) Practical Endocrinology and Diabetes in Children. Third edition. Wiley-Blackwell, Chichester.
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Test your knowledge: number 19
Growth hormone deficiency: part one How to use this assessment This self-assessment questionnaire will help you to test your knowledge. It comprises ten multiple choice questions that are broadly linked to the article starting on page 32. There is one correct answer to each question. You can test your subject knowledge by attempting the questions before reading the article, and then go back over them to see if you would answer any differently, or you might like to read the article before trying the questions. The answers will be published in the next issue of Nursing Children and Young People. When you have completed your self-assessment, cut out this page and add it to your professional portfolio. You can record the amount of time it has taken you to complete and add comments in the space provided. 1. In how many children of short stature does growth hormone deficiency (GHD) occur? One in: a) 2,500-3,000 b) 3,000-3,500 c) 3,500-4,000 d) 4,000-4,500 2. At what age does the importance of the hypothalamic-pituitary axis increase? a) 18 months b) Two years c) Five years d) Onset of puberty 3. Which protein does growth hormone help to produce? a) IGF-1 b) IGF-2 c) IGF-a d) IGF-b
7. Growth hormone binds to: a) Triglycerides b) Enterocytes c) Adipocytes d) Thymocytes
8. Growth hormone replacement works best when administered: a) Once a day in the morning b) Once a day in the evening c) Twice a day d) Every other day
9. In which year was the role of the pituitary gland in growth identified? a) 1886 b) 1920 c) 1956 d) 1958 10. How high do children with severe but untreated GHD usually grow? a) 110-120cm b) 120-130cm c) 130-140cm d) 140-150cm
This self-assessment questionnaire was compiled by Stephanie Jones-Berry
4. What percentage of patients are affected by isolated idiopathic GHD? a) 10-20% b) 30-45% c) 50-70% d) 75-80% 5. ‘Juvenilisation’ is risky for children because it: a) Lowers expectations by adults of their abilities b) Leads to isolation by their peers c) Limits opportunities to develop independent living skills d) All of the above
6. GHD therapy is recommended for: a) Turner syndrome b) Prader-Willi syndrome c) Chronic renal failure d) All of the above
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This activity has taken me article and completed this Excellent c Good
minutes/hours to complete. Now that I have read this assessment, I think my knowledge is: c Satisfactory c Unsatisfactory c Poor
c
As a result of this I intend to: _____________________________________________________ ______________________________________________________________________________ ______________________________________________________________________________ ______________________________________________________________________________ ______________________________________________________________________________ ______________________________________________________________________________ ______________________________________________________________________________ ______________________________________________________________________________ Answers to self-assessment questionnaire number 18 on the management of vitamin D deficiency in childhood and adolescence, published in the November issue of Nursing Children and Young People. 1. c, 2. d, 3. b, 4. c, 5. a, 6. a, 7. d, 8. d, 9. c, 10. b. February 2016 | Volume 28 | Number 1 37
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Educating children and families about growth hormone deficiency and its management: part 1 NCYP699 Collin J et al (2016) Educating children and families about growth hormone deficiency and its management: part 1. Nursing Children and Young People. 28, 1, 32-36. Date of submission: September 12 2015. Date of acceptance: November 17 2015. Correspondence [email protected]
Abstract The management of growth hormone deficiency is long term. Children may be diagnosed at pre-school age meaning relationships with the paediatric endocrine team may last more than 15 years. The education role of the paediatric endocrine nurse specialist is essential in working in partnership with families over a long period of time. Children and young people have changing needs for information to help them understand their condition and growth hormone deficiency treatment as they grow up. Developing positive working relationships with parents, children and young people enables their developmental needs and the context in which they live their lives to be central to any educational planning for them. Addressing developmental needs when providing information on growth hormone deficiency to children and young people reinforces the need for education to be an ongoing process and not a one-off event. This is part one of a two-part article. The second part will be published in the March issue of Nursing Children and Young People and it focuses on educating children, young people and their parents about the condition, and includes case studies.
Aims and intended learning outcomes The aim of this article is to examine how paediatric endocrine nurse specialists (PENS) meet the educational needs of children and young people and their parents following a diagnosis of growth hormone deficiency (GHD). This article will enable you to: ■ Review the function of growth hormone (GH). ■ Obtain an overview of the causes of GHD and clinical presentations. ■ Understand conditions where growth hormone therapy (GHT) is recommended. ■ Develop insight into the development of GHT. ■ Gain an overview of the importance of building partnerships with parents. GHD is the most common endocrine condition presenting in children with short stature, occurring in approximately one in 3,500-4,000 (National Institute for Health and Care Excellence (NICE) 2010, Raine et al 2011). Physiological replacement of GH is the treatment for this condition. Following diagnosis 32 February 2016 | Volume 28 | Number 1
children commence a daily subcutaneous injection/ transjection of synthetic recombinant human growth hormone (rHGH). GH replacement is necessary for these children to reach their target for final adult height (Martin and Collin 2015). Treatment continues for many years, often into adulthood. Successful outcomes for children, young people and their parents largely depend on a clear understanding of the condition and its long-term management. Educating and supporting children, young people and their families is an essential role of the PENS. Partnership working is key to enabling children and their families to manage the impact of this long-term treatment on their day-to-day lives, and promoting adherence with the management plan.
Jacqueline Collin is lecturer/ head of department, child and adolescent nursing, King’s College London Amanda Whitehead and Jenny Walker are children’s endocrine specialist nurses, Leeds Teaching Hospitals NHS Trust Keywords Child health, children development, endocrine nurse specialist, growth hormone deficiency, growth hormone therapy, paediatrics, parents Conflict of interest None declared Peer review This article has been subject to open peer review and checked using antiplagiarism software. For related articles visit our online archive and search using the keywords Author guidelines journals.rcni.com/r/ ncyp-author-guidelines
Role of growth hormone
GH is the main regulator of human growth ensuring all parts of the body, including organs, grow in proportion (Raine et al 2011). Nutrition has a dominant role in intrauterine growth, which means that infants with NURSING CHILDREN AND YOUNG PEOPLE
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idiopathic GHD are rarely identified at birth; however, from about two years of age the hypothalamic-pituitary axis becomes increasingly important with GH taking up its primary role in stimulating childhood growth and maintenance of tissues throughout the body (Raine et al 2011, Kirk 2012). The anterior pituitary gland synthesises and secretes GH. The process is regulated by neurosecretory nuclei of the hypothalamus (Raine et al 2011). These cells release peptides called growth hormone releasing hormone and somatostatin into the hypophyseal portal venous blood supply which surrounds the pituitary. GH release is pulsatile in nature, determined by a balance between these stimulating and inhibitory peptides. Additional influence comes from other physiological stimulators such as exercise and sleep or from inhibitors such as free fatty acids (Raine et al 2011). GH can be seen to affect growth directly, and most obviously, by acting on epiphyseal growth plates to produce linear growth, but it also acts indirectly by the production of growth factors (Laycock and Meeran 2013). In the liver GH stimulates production of a protein called insulin-like growth factor (IGF-1), which is the main mediator of many of the actions of GH. IGF-1 is responsible for promoting growth in the post-natal period. It stimulates cell division, thereby influencing cartilage cells at the end of long bones to multiply, which in turn lengthens the bone (Laing 2014). IGF-1 is the main GH-dependent growth factor and its measurement correlates well with spontaneous GH secretion and for this reason it is used in the diagnosis of GHD. Early identification of poor growth is important because GH has a profound effect on growth during the early years of life and will affect a child’s final adult height (Figure 1). Insufficient amounts of GH means children’s growth may be poor resulting in short stature (Laycock and Meeran 2013). As children reach puberty, the pubertal growth spurt is triggered by an increase in concentrations of GH in conjunction with sex hormones and insufficiency in these hormones will significantly affect the child’s final height. Puberty heralds the end of linear growth; consequently treatment has to be optimised before puberty. After puberty cartilage is converted to bone, meaning that IGF-1 will have little or no effect in further increasing bone length. GH stimulates growth and maintains general tissues in the body; however, not all of its functions are completely understood yet (Laycock and Meeran 2013). The process of growth is complex and involves the synthesis of molecules in all tissues of the body; hence, the influence of GH in the regulation of metabolism of proteins, lipids and carbohydrates throughout life (NICE 2010). NURSING CHILDREN AND YOUNG PEOPLE
Figure 1 Measuring children is important to assess the effects of growth hormone
Causes of growth hormone deficiency
Common causes of GHD are congenital, acquired or idiopathic (Kirk 2012). The vast majority of children diagnosed with GHD have no identifiable cause. This is described as isolated idiopathic GHD and accounts for 50-70% of patients (NICE 2010, Kirk 2012). More boys present with GHD than girls, although the reason for this is not known. GHD is not always isolated and can be associated with other anterior and posterior pituitary hormone deficiencies arising from hypopituitarism (Raine et al 2011); for example, thyroid stimulating hormone may be affected or adrenocorticotropic hormone. There are familial forms of GHD: autosomal recessive, autosomal dominant or X-linked recessive, which determine the severity of the condition. Children can also develop acquired GHD which may occur as a result of injury, infection or tumour growth in the hypothalamic pituitary region such as craniopharyngiomas (Dattani and Preece 2004). Treatment of tumour growth by surgery or cranial irradiation may cause some damage to the pituitary gland which then fails to function adequately putting children at risk of GHD. The terms GHD or insufficiency are often used interchangeably, however, they are different and reflect the nature of the child’s problem – deficiency relates to very low levels whereas insufficiency refers to inadequate GH production. Other reasons for growth failure in children are identified in Box 1. February 2016 | Volume 28 | Number 1 33
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Continuing professional development Box 1 Conditions where growth hormone therapy is recommended ■ Growth hormone deficiency ■ Turner syndrome ■ Prader-Willi syndrome. ■ Growth failure at four years or older and born small for gestational age ■ Short stature homeobox – containing gene (SHOX) deficiency. ■ Chronic renal insufficiency.
Not all children present in exactly the same way because this will depend on the cause of their GHD (Kirk 2012). Invasive investigations to confirm a diagnosis of GHD are undertaken when all other possibilities have been excluded. Initial investigations commonly undertaken are summarised in Box 2. Growth hormone has a peak concentration during a child’s sleep and, therefore, the treatment using GH replacement works most effectively when administered once a day in the evening. Now do time out 1
Not all children and young people who are short have a GHD. Healthy children whose family is shorter than average may have a height appropriate for their genetic background. Other children may be referred because they are shorter and their sexual maturation is delayed. This is described as constitutional delay. Typically they will reach their adult height albeit later than their peers. Treatment with GH for these children is an area of professional and ethical debate (Morrison 2015). Referral to specialist endocrine services is usually triggered by concerns of parents or community health practitioners in relation to short stature, absent or very low rate of growth (Martin and Collin 2015). GH binds to adipocytes and causes them to break down triglycerides affecting fat storage in the body, hence children with GHD tend to have a greater weight to height ratio and may appear overweight. Slow growth may be noticed during infancy, but is more commonly noticed from the age of two years, although a referral may occur at any time during childhood. Commonly parents become aware that their child is in younger clothes sizes and is significantly smaller than their peers. An unexpected growth pattern is recognised in the sequential measurements recorded since birth and healthcare professionals trigger referral for investigation. Although very short, children with GHD have normal body proportions and parents can be reassured that the child’s intellect is unaffected. Physical development is delayed and children may look younger than they are as their skeletal maturity/bone age is delayed; for example, immature growth of the skull means the child will have facial proportions of a younger child described as midfacial hypoplasia, small hands and feet and hypoglycaemia may occur in neonates (Kirk 2012). Children may be treated and spoken to as though they are younger than their chronological age. Erling (2004) describes ‘juvenilisation’ as a risk factor for the emotional and social development of children with short stature because of lower expectations by adults of their abilities, isolation by their peers and limited opportunities to develop independent living skills, which potentially erodes their confidence and sense of autonomy. 34 February 2016 | Volume 28 | Number 1
1
Warning signs
Time out
(National Institute for Health and Care Excellence 2010)
Describe the concerns and cues that would alert parents and healthcare professionals to refer a child to specialist endocrine services?
Growth hormone therapy
Replacement therapy has not always been as straightforward as it is now. Tattersall (1996) reports that the importance of the pituitary gland in relation to growth was first identified in 1886 when Pierre Marie (1853-1940) reviewed reported cases of acromegaly and made a connection with pituitary tumours. Further experiments throughout the 1920s and 1930s added weight to these early findings and, by the 1940s, bovine and porcine GH was successfully isolated. However, this was not useful in the treatment of GHD in children because it became clear that GH was species specific (Tattersall 1996); only human growth hormone (HGH) from human pituitaries could produce growth in children (Morrison 2015). The supply of HGH was limited as Box 2 Initial investigations ■ Review of previous weight and height on standardised growth charts ■ Target centile range using parental heights ■ Calculation of growth rate ■ Bone age of left hand and wrist ■ Magnetic resonance imaging of the head ■ Baseline blood testing ■ Pituitary testing consisting of stimulation tests which are designed to stimulate the production of GH. NICE guidelines state that a diagnosis of GHD requires two GH provocation (stimulation) tests to be performed. The diagnostic testing involved is discussed in detail in the third article in this series, which explains clinical investigations (National Institute for Health and Care Excellence 2010, Davies and Collin 2015)
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Table 1 Supply of recombinant human growth hormone (somatropin) Company
Growth hormone
Device/s
Pfizer
Genotropin
Genotropin pen/ Genotropin miniquick
Novo Nordisk
Norditropin simpleXx
Nordipen/ Nordiflex
Merck Serono
Saizen
Easypod
Ferring
Zomacton
Zomajet
Sandoz
Omnitrope
Surepal
Ipsen
NutropinAq
NutropinAq pen
Eli Lilly
Humatrope
Humatropen
GH and states, for example: ‘The dosage varies according to the condition being treated: 23-39 microgram/kg daily or 0.7–1.0 mg/m2 daily for GHD’. The growth response of the products from the different companies is the same; however, differences exist in the injection devices and support services offered. These differences contribute to decisions families make about devices they ultimately choose. The majority of centres offer an open choice of device, although there may be local differences that would be clarified by the PENS. Most GH in the UK is prescribed on a shared care basis between primary, secondary and tertiary care, with GPs taking responsibility for prescribing and the lead centre taking responsibility for the initial diagnosis, monitoring and adjustment of therapy (Kirk 2012). PENS liaise to facilitate communication between specialist and primary health care services to ensure any changes to GHT are seamless for families (Jones 2014). Now do time out 2
2
True or false?
Time out
it could only become available from pituitary glands from cadavers (Tattersall 1996). In 1956 American biochemists first isolated HGH from human pituitary glands and in 1958 its first clinical use successfully illustrating increased growth rate and height in childhood GHD was reported (Kirk 2012). Regulatory bodies were set up – the National Pituitary Agency in the United States and the Medical Research Council in the United Kingdom. A pituitary hormone committee was organised to develop clinical trials to examine the potential of HGH as a treatment for children with extreme short stature (Morrison 2015). Limited availability of HGH meant that only children with severe short stature were treated. Two important events occurred in 1985 that would change this situation. The first was withdrawal of HGH following reported cases of a fatal neurological disease – Creutzfeldt-Jakob disease – diagnosed in patients who had been treated from the 1960s. Potentially many people could be infected from one batch of GH, which was formed from up to 2,000 human pituitary glands, pooled and divided into individual doses for distribution. Later that year a biosynthetic version of GH – rHGH – became available for clinical use. Recombinant technology involves the insertion of genes into cells that solved the problem of disease transmission and addressed the limited supply (Kirk 2012, Morrison 2015). Until this point only the most severely affected children were treated, but since 1985 all children with inadequate levels of GH have had an opportunity to receive replacement therapy. However, parents may not always have the same view as their children about GHD and GHT, which may affect adherence in the long term (Upton et al 2008). Research with children aged more than ten years, focusing on the implications of parent and child quality of life assessments underpinning decisions about GHT, identified that many clinical decisions are based on the presumption of ‘future benefits rather than current disadvantages’ (Otero et al 2103). The advice from NICE (2010) is children’s views about GHT and their perceptions about their short stature need to be discussed with them to inform the treatment decision. Children with severe GHD who are left untreated can have a final height of 130-140cm (Kirk 2012). The main purpose of treatment is to normalise growth. GH is licensed by NICE to treat specific childhood conditions identified in Box 1. Several pharmaceutical companies are involved in the development and production of rHGH. Each product is produced by recombinant DNA technology and has a sequence identical to HGH (NICE 2010). There are currently seven preparations of somatropin available in the UK, listed in Table 1. Treatment is individualised to meet the requirement of each child. NICE (2010) provides guidance for the use of
Which of the following statements are true or false? 1. Human growth hormone is species specific. 2. Recombinant technology involves insertion of genes into cells and prevents transmission of disease. 3. The primary aim of growth hormone therapy is to improve bone density. 4. In the UK the licence for growth hormone means children diagnosed with growth hormone deficiency, Turner syndrome and chronic renal insufficiency are eligible for growth hormone therapy. 5. The growth response of different products varies.
February 2016 | Volume 28 | Number 1 35
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Continuing professional development The long-term nature of GHT means that parents experience a burden of care that poses challenges at different ages and stages of their child’s development (Kremidas et al 2013, Otero et al 2013). The primary aim for PENS is to develop a therapeutic relationship with parents from the outset. The timing of the first meeting with families will vary. For some it may be within the investigative period, for others it may be when the diagnosis is confirmed, or later, at a home visit to teach families about GHD and commence treatment. However, the primary aim remains: to establish a therapeutic relationship leading to partnership working, enabling families to be empowered and self-assured in balancing their child’s medical and developmental needs. In Western culture being tall is perceived as a positive characteristic, whereas being short is seen as less desirable. Social stereotypes related to height are established at an early age and are considered to result in social stigma (Voss and Sandberg 2004). However, although short stature does not always result in negative psychosocial experiences for children and young people (Erling 2004, Otero et al 2013), it is an anxiety frequently expressed by parents. To develop a helping relationship with parents, an empathetic approach is needed by the PENS. Individual concerns can be addressed, while maintaining an objective approach to planning, teaching and supporting care at home. Information sharing and education is central to collaborative working with parents, enabling them to develop their expertise in parenting their children with GHD. Commencing GHT is a pivotal point in the development of relationships lasting many years between children, parents, the endocrine team and the PENS. Part 2 explores the role of PENS in educating families in relation to the management of GHT.
Conclusion
The medical management of GHD in children and young people significantly changed once GH replacement therapy became widely available in 1985. GHD is a long-term condition and the PENS is pivotal to education and support of families. When normalising growth through GHT, successful outcome is gradual, and children and young people subjected to daily injections may find this frustrating. The skill of the PENS lies in maintaining the engagement of parents, children and young people over many years, to promote a successful treatment outcome that makes the years of physical, emotional and social investment in their growth worthwhile. Now do time out 3
3 Time out
Partnerships with parents
Reflective account Now that you have completed this article you may want to complete the questionnaire on page 37 and write a reflective account of between 750-1,000 words. Go to journals.rcni.com/r/ ncyp-reflective-account to find out more. If you are an online subscriber, you can place these in your portfolio.
Answers to time out 2 1. True, 2. True, 3. False, 4. True, 5. False
Online archive For related information, visit our online archive and search using the keywords
References Dattani M, Preece M (2004) Growth hormone deficiency and related disorders: insights into causation, diagnosis, and treatment. The Lancet. 363, 9425, 1977-1987. Davies K, Collin J (2015) Understanding clinical investigations in children’s endocrinology. Nursing Children and Young People. 27, 8, 26-36. Erling A (2004) Why do some children of short stature develop psychologically well while others have problems? European Journal of Endocrinology. 151, Suppl 1, S35-S39. Jones J (2014) A strong relationship for a long journey. British Journal of Nursing. 23, Suppl 6, S10-S11.
Kirk J (2012) Indications for growth hormone therapy in children. Archives of Disease in Childhood. 97, 1, 63-68. Kremidas D et al (2013) Administration burden associated with recombinant human growth hormone treatment: perspectives of patients and caregivers. Journal of Pediatric Nursing. 28, 1, 55-63. Laing P (2014) Growth failure and hormone therapy. British Journal of Nursing. 23, Suppl 6, S3-S9. Laycock J, Meeran K (2013) Integrated Endocrinology. Wiley-Blackwell, Chichester. Martin L, Collin J (2015) An introduction to growth and atypical growth in childhood and adolescence. Nursing Children and Young People. 27, 6, 29-37.
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Morrison M (2015) Growth hormone, enhancement and the pharmaceuticalisation of short stature. Social Science and Medicine. 131, 305-312. National Institute for Health and Care Excellence (2010) Human Growth Hormone (Somatropin) for the Treatment of Growth Failure in Children: Technology Appraisal Guidance TA188. NICE, London. Otero SC et al (2013) Implications of parent and child quality of life assessments for decisions about growth hormone treatment in eligible children. Child: Care, Health and Development. 39, 6, 782-788.
Tattersall R (1996) A history of growth hormone. Hormone Research. 46, 4-5, 236-247. Upton P et al (2008) Parent-child agreement across child health-related quality of life instruments: a review of the literature. Quality of Life Research. 17, 6, 895-913. Voss LD, Sandberg DE (2004) The psychological burden of short stature: evidence against. European Journal of Endocrinology. 151, Suppl 1, S29-S33.
Raine JE et al (2011) Practical Endocrinology and Diabetes in Children. Third edition. Wiley-Blackwell, Chichester.
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Test your knowledge: number 19
Growth hormone deficiency: part one How to use this assessment This self-assessment questionnaire will help you to test your knowledge. It comprises ten multiple choice questions that are broadly linked to the article starting on page 32. There is one correct answer to each question. You can test your subject knowledge by attempting the questions before reading the article, and then go back over them to see if you would answer any differently, or you might like to read the article before trying the questions. The answers will be published in the next issue of Nursing Children and Young People. When you have completed your self-assessment, cut out this page and add it to your professional portfolio. You can record the amount of time it has taken you to complete and add comments in the space provided. 1. In how many children of short stature does growth hormone deficiency (GHD) occur? One in: a) 2,500-3,000 b) 3,000-3,500 c) 3,500-4,000 d) 4,000-4,500 2. At what age does the importance of the hypothalamic-pituitary axis increase? a) 18 months b) Two years c) Five years d) Onset of puberty 3. Which protein does growth hormone help to produce? a) IGF-1 b) IGF-2 c) IGF-a d) IGF-b
7. Growth hormone binds to: a) Triglycerides b) Enterocytes c) Adipocytes d) Thymocytes
8. Growth hormone replacement works best when administered: a) Once a day in the morning b) Once a day in the evening c) Twice a day d) Every other day
9. In which year was the role of the pituitary gland in growth identified? a) 1886 b) 1920 c) 1956 d) 1958 10. How high do children with severe but untreated GHD usually grow? a) 110-120cm b) 120-130cm c) 130-140cm d) 140-150cm
This self-assessment questionnaire was compiled by Stephanie Jones-Berry
4. What percentage of patients are affected by isolated idiopathic GHD? a) 10-20% b) 30-45% c) 50-70% d) 75-80% 5. ‘Juvenilisation’ is risky for children because it: a) Lowers expectations by adults of their abilities b) Leads to isolation by their peers c) Limits opportunities to develop independent living skills d) All of the above
6. GHD therapy is recommended for: a) Turner syndrome b) Prader-Willi syndrome c) Chronic renal failure d) All of the above
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This activity has taken me article and completed this Excellent c Good
minutes/hours to complete. Now that I have read this assessment, I think my knowledge is: c Satisfactory c Unsatisfactory c Poor
c
As a result of this I intend to: _____________________________________________________ ______________________________________________________________________________ ______________________________________________________________________________ ______________________________________________________________________________ ______________________________________________________________________________ ______________________________________________________________________________ ______________________________________________________________________________ ______________________________________________________________________________ Answers to self-assessment questionnaire number 18 on the management of vitamin D deficiency in childhood and adolescence, published in the November issue of Nursing Children and Young People. 1. c, 2. d, 3. b, 4. c, 5. a, 6. a, 7. d, 8. d, 9. c, 10. b. February 2016 | Volume 28 | Number 1 37
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