Editorial-Growth and Its Disorders
http://www.100md.com
《美国医学杂志》
Department of Pediatrics,Armed Forces Hospital, Kuwait
The growth hormone and insulin like growth factors (GH-IGF) play a vital role in the regulation of growth. The GH-IGF axis includes the hypothalamic-pituitary axis (responsible for production of GH), GH receptors (responsible for IGF production), IGF binding proteins (IGFBP, responsible for transport of IGF) and IGF receptors (responsible for IGF action). Insulin like growth factors were initially considered to be mediators of GH action but are now considered to be independent endocrine factors which influence a number of biological processes. Recent advances have led to tremendous increase in the clinical utility of the GH-IGF axis. IGF- based investigations (IGF1 and IGFBP 3) are now replacing GH-based investigations for evaluation and monitoring of disorders of the GH-IGF axis, including GH deficiency and insensitivity. IGF therapy has been successfully utilized in growth hormone insensitivity syndrome and GH deficiency type 1B. The possibility of IGF axis as a therapeutic option is being explored in other disorders. Anurag Bajpai and P S N Menon discuss the details of GH-IGF axis in this symposium.[1]
David Zlotkin and S K Varma highlight the psychosocial effects of short stature and the nonlinear benefits of GH therapy in this issue.[2] The number of adolescents seeking advice and help from clinicians regarding modalities for improving height is on the rise. Beauty pageants and sports have created a niche for tall stature in the society and every child now yearns to be tall, attractive and handsome. Attention to the potential psychological or behavioral concerns of short children and adolescents is very important. Short adolescents develop low self-esteem and emotional immaturity as most of them are treated as children and not as adolescents. Children with short stature have several psychological disadvantages, and short stature itself, not the underlying disorder, can have significant impact on the short child and adolescent.[3] Prompt therapy can help to restore their confidence and self-esteem, and social functioning. Such benefits can tilt the balance towards a safe but expensive GH therapy for short children.
3-10% babies worldwide are born small for gestational age (SGA). About 85-90% babies who are born SGA show catch-up growth soon after birth. 10% of SGA babies fail to show catch-up growth despite good nutrition after birth. SGA children usually enter puberty slightly earlier than their peers. Accelerated bone maturation during puberty may be present. Growth spurt during puberty is blunted compared to other adolescents. All these could result in worsening of their short stature. Long term follow-up of babies born SGA reveal that they are at a higher risk of developing metabolic problems later in life, such as impaired glucose tolerance, type 2 diabetes mellitus, metabolic syndrome, hypertension, dyslipidemia and cardiovascular disease. Infants who do not show catch-up growth usually have an alteration in the GH-IGF-I axis. GH has been used to help short SGA children achieve catch-up growth. A number of multicenter trials have been carried with GH therapy for SGA babies who do not show catch-up growth over the last few years. GH was used irrespective of their GH status. Both high and low dose GH and continuous and discontinuous treatment have been used in these children. The studies revealed that GH was an effective treatment for normalizing short stature in non-GH deficient SGA children during early childhood and puberty. Both low dose continuous and high dose discontinuous therapy with GH were equally effective. Benefits of GH therapy are similar in GH deficient and non-GH-deficient SGA children. Archana D Arya discusses the issues related to short stature and GH therapy in SGA children in this issue.[4]
Poor growth in precocious puberty is a subject of concern to patients, their families and clinicians. The definition of precocious puberty and the role of obesity in the age of onset have been areas of debate. The Lawson Wilkins Pediatric Endocrine Society recommended a lowering of the age of onset of precocious puberty in US girls. As per new guidelines, breast development or pubic hair development occurring before the age of 7 in white girls and before the of age 6 in African-American girls should be evaluated.[5] A clear understanding of growth patterns in normal children with earlier and later onset of puberty and the variable rate of progression between individuals with central precocious puberty is essential for decision-making on various treatment options. GnRH agonist analogs have become the treatment of choice due to effective suppression of pituitary gonadotropin secretion and gonadal sex steroid secretion. A number of studies have now reported final height in treated patients.[6] Height prediction in PP is difficult and often imprecise with tendency for overestimation. The exact benefit is difficult to assess, but the mean increase in adult height in girls is at least 5 cm, and probably more.[6] There appears to be no benefit in treating girls above 8 years of age and those with slowly progressive precocious puberty. The treatment benefits for boys are less clear, but compared to historical controls, final height appears to be improved. The decision to treat central precocious puberty should take into account the rate of progression of pubertal changes as well as biochemical markers and may need to address other factors (psychosocial and behavioral issues) as well as height outcome. J J Brown and G L Warne discuss these issues in detail in this issue.[7]
Individuals with congenital adrenal hyperplasia (CAH) are shorter, on average, than the general population. The height deficit is typically 1 to 2 SD below the mean in both boys and girls. Growth in CAH due to 21-hydroxylase deficiency is influenced by a number of factors related to the underlying disease and its treatment. Better height outcomes are seen in patients with non-classic CAH, early diagnosis, adequate treatment and good compliance. In general, boys with the simple virilising (SV) form have the poorest height prognosis. Reduced final height in the SV form may be related to late detection and consequent prolonged exposure to androgen excess, advanced bone age and early puberty in these patients. Obesity in CAH patients also appears to be correlated with reduced height potential. Optimization of current treatment may lead to further improvements in height prognosis. Administration of glucocorticoids which are vital for cortisol replacement, prevention of adrenal crises and androgen suppression, results in growth inhibition when given in larger doses. Standard cortisol replacement schedules and dose titration to achieve complete androgen suppression and normalization of 17-hydroxyprogesterone are likely to result in overtreatment and consequent growth impairment. To avoid adverse effects, dosing should be adjusted to maintain 17-OHP at a level slightly higher than normal.[8] The potential benefits of more complex treatment regimes using aromatase inhibitors and antiandrogens in combination with a reduced glucocorticoid dose remain uncertain. An T T Nguyen et al review the literature on height outcome in CAH and consider factors related to diagnosis and treatment which are known to affect height outcome and discuss current strategies to optimise height outcome.[9]
References
1. Bajpai A, Menon PSN. Insulin like growth factors axis and growth disorders. Indian J Pediatr 2006; 73: 67-71.
2. Zlotkin D, Varma SK. Psychosocial effects of short stature. Indian J Pediatr 2006; 73: 79-80.
3. Steinhausen HC, Dorr HG, Kannenberg R, Malin Z. The behavior profile of children and adolescents with short stature. J Devel Behav Pediatr 2000; 21: 423-428.
4. Arya AD. Small for Gestation and GH Therapy. Indian J Pediatr 2006; 73 : 73-78.
5. Kaplowitz PB, Oberfield SE. Reexamination of the age limit for defining when puberty is precocious in girls in the United States: implications for evaluation and treatment. Drug and Therapeutics and Executive Committees of the Lawson Wilkins Pediatric Endocrine Society. Pediatrics 1999; 104: 936-941.
6. Bajpai A, Sharma J, Kabra M, Gupta AK, Menon PSN. Long-acting GnRH analogue triptorelin therapy in central isosexual precocious puberty. Indian Pediatr 2002; 39: 633-639.
7. Brown JJ, Warne GL. Growth in Precocious Puberty. Indian J Pediatr 2006; 73 : 81-88.
8. Speiser PW, White PC. Congenital adrenal hyperplasia. New Eng J Med 2003; 349 : 776-788.
9. Nguyen ATT, Brown JJ, Warne GL. Growth in Congenital Adrenal Hyperplasia. Indian J Pediatr 2006; 73: 89-93.(Menon P S. N)
The growth hormone and insulin like growth factors (GH-IGF) play a vital role in the regulation of growth. The GH-IGF axis includes the hypothalamic-pituitary axis (responsible for production of GH), GH receptors (responsible for IGF production), IGF binding proteins (IGFBP, responsible for transport of IGF) and IGF receptors (responsible for IGF action). Insulin like growth factors were initially considered to be mediators of GH action but are now considered to be independent endocrine factors which influence a number of biological processes. Recent advances have led to tremendous increase in the clinical utility of the GH-IGF axis. IGF- based investigations (IGF1 and IGFBP 3) are now replacing GH-based investigations for evaluation and monitoring of disorders of the GH-IGF axis, including GH deficiency and insensitivity. IGF therapy has been successfully utilized in growth hormone insensitivity syndrome and GH deficiency type 1B. The possibility of IGF axis as a therapeutic option is being explored in other disorders. Anurag Bajpai and P S N Menon discuss the details of GH-IGF axis in this symposium.[1]
David Zlotkin and S K Varma highlight the psychosocial effects of short stature and the nonlinear benefits of GH therapy in this issue.[2] The number of adolescents seeking advice and help from clinicians regarding modalities for improving height is on the rise. Beauty pageants and sports have created a niche for tall stature in the society and every child now yearns to be tall, attractive and handsome. Attention to the potential psychological or behavioral concerns of short children and adolescents is very important. Short adolescents develop low self-esteem and emotional immaturity as most of them are treated as children and not as adolescents. Children with short stature have several psychological disadvantages, and short stature itself, not the underlying disorder, can have significant impact on the short child and adolescent.[3] Prompt therapy can help to restore their confidence and self-esteem, and social functioning. Such benefits can tilt the balance towards a safe but expensive GH therapy for short children.
3-10% babies worldwide are born small for gestational age (SGA). About 85-90% babies who are born SGA show catch-up growth soon after birth. 10% of SGA babies fail to show catch-up growth despite good nutrition after birth. SGA children usually enter puberty slightly earlier than their peers. Accelerated bone maturation during puberty may be present. Growth spurt during puberty is blunted compared to other adolescents. All these could result in worsening of their short stature. Long term follow-up of babies born SGA reveal that they are at a higher risk of developing metabolic problems later in life, such as impaired glucose tolerance, type 2 diabetes mellitus, metabolic syndrome, hypertension, dyslipidemia and cardiovascular disease. Infants who do not show catch-up growth usually have an alteration in the GH-IGF-I axis. GH has been used to help short SGA children achieve catch-up growth. A number of multicenter trials have been carried with GH therapy for SGA babies who do not show catch-up growth over the last few years. GH was used irrespective of their GH status. Both high and low dose GH and continuous and discontinuous treatment have been used in these children. The studies revealed that GH was an effective treatment for normalizing short stature in non-GH deficient SGA children during early childhood and puberty. Both low dose continuous and high dose discontinuous therapy with GH were equally effective. Benefits of GH therapy are similar in GH deficient and non-GH-deficient SGA children. Archana D Arya discusses the issues related to short stature and GH therapy in SGA children in this issue.[4]
Poor growth in precocious puberty is a subject of concern to patients, their families and clinicians. The definition of precocious puberty and the role of obesity in the age of onset have been areas of debate. The Lawson Wilkins Pediatric Endocrine Society recommended a lowering of the age of onset of precocious puberty in US girls. As per new guidelines, breast development or pubic hair development occurring before the age of 7 in white girls and before the of age 6 in African-American girls should be evaluated.[5] A clear understanding of growth patterns in normal children with earlier and later onset of puberty and the variable rate of progression between individuals with central precocious puberty is essential for decision-making on various treatment options. GnRH agonist analogs have become the treatment of choice due to effective suppression of pituitary gonadotropin secretion and gonadal sex steroid secretion. A number of studies have now reported final height in treated patients.[6] Height prediction in PP is difficult and often imprecise with tendency for overestimation. The exact benefit is difficult to assess, but the mean increase in adult height in girls is at least 5 cm, and probably more.[6] There appears to be no benefit in treating girls above 8 years of age and those with slowly progressive precocious puberty. The treatment benefits for boys are less clear, but compared to historical controls, final height appears to be improved. The decision to treat central precocious puberty should take into account the rate of progression of pubertal changes as well as biochemical markers and may need to address other factors (psychosocial and behavioral issues) as well as height outcome. J J Brown and G L Warne discuss these issues in detail in this issue.[7]
Individuals with congenital adrenal hyperplasia (CAH) are shorter, on average, than the general population. The height deficit is typically 1 to 2 SD below the mean in both boys and girls. Growth in CAH due to 21-hydroxylase deficiency is influenced by a number of factors related to the underlying disease and its treatment. Better height outcomes are seen in patients with non-classic CAH, early diagnosis, adequate treatment and good compliance. In general, boys with the simple virilising (SV) form have the poorest height prognosis. Reduced final height in the SV form may be related to late detection and consequent prolonged exposure to androgen excess, advanced bone age and early puberty in these patients. Obesity in CAH patients also appears to be correlated with reduced height potential. Optimization of current treatment may lead to further improvements in height prognosis. Administration of glucocorticoids which are vital for cortisol replacement, prevention of adrenal crises and androgen suppression, results in growth inhibition when given in larger doses. Standard cortisol replacement schedules and dose titration to achieve complete androgen suppression and normalization of 17-hydroxyprogesterone are likely to result in overtreatment and consequent growth impairment. To avoid adverse effects, dosing should be adjusted to maintain 17-OHP at a level slightly higher than normal.[8] The potential benefits of more complex treatment regimes using aromatase inhibitors and antiandrogens in combination with a reduced glucocorticoid dose remain uncertain. An T T Nguyen et al review the literature on height outcome in CAH and consider factors related to diagnosis and treatment which are known to affect height outcome and discuss current strategies to optimise height outcome.[9]
References
1. Bajpai A, Menon PSN. Insulin like growth factors axis and growth disorders. Indian J Pediatr 2006; 73: 67-71.
2. Zlotkin D, Varma SK. Psychosocial effects of short stature. Indian J Pediatr 2006; 73: 79-80.
3. Steinhausen HC, Dorr HG, Kannenberg R, Malin Z. The behavior profile of children and adolescents with short stature. J Devel Behav Pediatr 2000; 21: 423-428.
4. Arya AD. Small for Gestation and GH Therapy. Indian J Pediatr 2006; 73 : 73-78.
5. Kaplowitz PB, Oberfield SE. Reexamination of the age limit for defining when puberty is precocious in girls in the United States: implications for evaluation and treatment. Drug and Therapeutics and Executive Committees of the Lawson Wilkins Pediatric Endocrine Society. Pediatrics 1999; 104: 936-941.
6. Bajpai A, Sharma J, Kabra M, Gupta AK, Menon PSN. Long-acting GnRH analogue triptorelin therapy in central isosexual precocious puberty. Indian Pediatr 2002; 39: 633-639.
7. Brown JJ, Warne GL. Growth in Precocious Puberty. Indian J Pediatr 2006; 73 : 81-88.
8. Speiser PW, White PC. Congenital adrenal hyperplasia. New Eng J Med 2003; 349 : 776-788.
9. Nguyen ATT, Brown JJ, Warne GL. Growth in Congenital Adrenal Hyperplasia. Indian J Pediatr 2006; 73: 89-93.(Menon P S. N)