Psychosocial effects of short stature
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《美国医学杂志》
Department of Pediatrics, Texas Tech University Health Sciences Center, Lubbock, USA
Abstract
The treatment of children with short stature was revolutionized by the creation of recombinant growth hormone therapy. While it cannot be denied that therapy adds significant height to children who are growth hormone deficient, such treatment is both painful, requiring many injections for years, as well as extremely expensive, both for the children's parents as well as for medical health care for society. With the indications for growth hormone treatment expanding over the years to include children with short stature who are not growth hormone deficient, it is important to determine all potential benefits beyond the obvious physical effects in order to make efficient cost-benefit determinations on appropriate usage of growth hormone therapy. One aspect of possible benefits for these children with short stature may be psychological features, such as increased overall happiness and self-esteem that is gained with increased height. A review and analysis of literature was undertaken in order to determine what effect, if any, growth hormone therapy has on short children's psychosocial well-being.
Keywords: Short stature; Growth hormone; Psychological
Since the introduction of recombinant growth hormone (GH) therapy in 1985, a vast number of children have undertaken therapy to improve their eventual adult height. With cost of such treatment exceeding $20,000 per year for several years, many third-party payers have shown reluctance in providing such treatment. While it is well established that GH therapy will have a positive effect on height, the impact on psychological factors is less proven. It has been assumed that children of short stature experience behavioral disorders secondary to adverse social experiences and that an increase in height would alleviate these events, resulting in adults that would have greater cognitive functioning than they would have if they were not treated. If this hypothesis was proven to be valid, the overall financial cost of GH therapy would be lessened, both by the reduced amount of psychological services required by these children as well as the increased productivity and contribution to society as higher functioning adults. In order to determine the non-linear effect of GH therapy, a review and analysis of the literature was undertaken.
During the literature review process, many studies were examined in order to validate the hypothesis that GH therapy would have a beneficial effect on the psychological aspects of children. Several early psychological studies of children with short stature showed an increased percentage of problems, including social aversion, anxiety, and attention problems when compared to controls. However, in these studies, children were usually described as 'dwarfs' or 'hypopituitary children', making it difficult to discern if the children studied had isolated GH deficiency (GHD) or suffered from other genetic or medical conditions, which can also contribute to potential psychological problems.[1]
Other studies were performed by surveying adults that were treated for GHD as children and comparing their quality of life measures to the general population. While the GH treated adults were less likely to be married, perform well in school, or gain meaningful employment, the exact clinical psychological impact of these results are difficult to interpret[2] .
Stabler et al[3] compared 195 children of short stature with a control group and measured the prevalence of behavioral and learning problems. The children were further classified as being GHD or idiopathic short stature (ISS) via responsiveness to stimulation testing. Overall, a greater number of short stature children had difficulty in school and suffered from behavioral problems than those of controls. No differences were observed specifically between the GHD group and those of ISS. There were no statistically significant differences in academic achievement observed between the two groups. After three years of GH therapy in both the groups, both showed improvement in an overall psychological functioning as measured by the Total Behavior Problem scale. Those with GHD, however, showed significant improvement in 7 out of the 8 individual factors, as compared to 2 for ISS, with both groups improving in the Anxious/Depressed and Social Problems subscales. These results mirror those performed on GHD adults, who have been described as more socially isolated and less energetic than GH sufficient controls.
In their study, Erling et al[4] compared sixty short stature children using the Visual Analogue Scale for Children (VASC), again separating GHD children from ISS by stimulation testing. The group of children who were GHD had a more negative self-perception of their physical appearance than compared to controls, which was not seen when those with ISS were compared to those of normal stature, perhaps due to the other physical effects of GHD on muscle formation and adipose deposition in tissues. The authors then took the next step of correlating the maximum amount of GH stimulated during testing to the same VASC subscales. The results showed a strong negative correlation between the maximal GH amount of the children and the inhibition subscale, stating that the children that have the least amount of GH were described as being more inhibited by both the children themselves as well as their parents. It has been theorized that since the neuro-endocrine centers that modulate mood and affect are functionally related to GH secretion by the pituitary, that decreased amounts of GH available would have a negative effect on these psychological factors.[5] This theory may explain the lower social skills achieved by GHD adults which have been consistently revealed by other studies[6] .
Van Pareren et al[7] examined children born small for gestational age (SGA) in the Netherlands, treated them with GH, and followed them for two and eight years, obtaining psychological values at baseline as well as each follow-up visit. The children were not divided between GHD and ISS. At baseline, the SGA children showed lower values in performance IQ as compared to population controls. This value improved significantly at two years post-GH therapy and at eight years was at par with the average Dutch samples. This effect was also seen in other areas, such as behavioral problems, which decreased from above the norm at baseline to average values. The most dramatic effect was seen in the mean self-perception scale, where the SGA children showed values well below the mean at baseline, was equivalent at two years post-treatment, and actually exceeded the average at eight years post GH therapy.
Finally, Wiren et al[8] took the next step by following adolescents who had been treated for GHD after their treatments were terminated due to their achievement of total adult height. These young adults were studied over a two year period to determine if the abrupt cessation of GH had a negative psychological effect. The data was further separated into those with GHD and those classified as GH sufficient, which is equivalent to the ISS category. While those with GHD had a decline in sociability and an increase in anxiety, not seen in the ISS group, there was no measurable decline in overall quality of life in either group of subjects. Therefore, any potential psychological gain made during GH therapy does not appear to deteriorate once therapy had ceased.
While the above studies were performed using various methods, the conclusions drawn state that GHD children are at higher risk for social difficulties and anxiety disorders, even greater than those with ISS. With GH therapy through to final adult height, these risks appear to be lessened and remain so through adulthood after GH discontinuation. Whether this is a direct effect of GH on the hypothalamic-pituitary axis or by increased social value associated with greater height is a question for further studies to answer. At the very least, the data shows that there are effects of GH therapy on GHD children that expand beyond the increase in final adult height and these factors should be taken into consideration when they are prescribed for these children.
References
1. Steinhausen H, Stahnke N. Psychendocrinological studies in dwarfed children and adolescents. Arch Dis Child 1976; 51: 778-783.
2. Bjork S, Jonsson B, Westphal O, Levin J-E. Quality of life of adults with growth hormone deficiency: a controlled study. Acta Paediatr Scand 1989; 356 (Suppl): 55-59.
3. Stabler B, Clopper RR, Siegel PT, Stoppani C, Compton PG, Underwood LE. Academic achievement and psychological adjustment in short children. J Dev Behav Pediatr 1994; 15: 1-6.
4. Erling A, Wiklund I, Wikland K. Psychological functioning in boys of short stature: effects of different levels of growth hormone secretion. Acta Paediatr 2002; 91: 966-971.
5. Abelson JL, Glitz D, Cameron OG, Lee MA, Bronzo M, Curtis GC. Blunted growth hormone response to clonidine in patients with generalized anxiety disorder. Arch Gen Psychiatr 1991; 48(2): 157-162.
6. Barker DJ, Erikkson JG, Forsen T, Osmond C. Infant growth and income 50 years later. Arch Dis Child 2005; 90(3): 272-273.
7. van Pareren, YK, Duivenvoorden FS, Slijper FS, Koot HM, Hokken-Koelega AC. Intelligence and psychological functioning during long-term growth hormone therapy in children born small for gestational age. J Clin Endocrinol Metab 2004; 89(11): 5295-5302.
8. Wiren L, Johnannson G, Bengtsson B. A prospective Investigation of quality of life and psychological well-being after the discontinuation of GH treatment in adolescent patients who had GH deficiency during childhood. J Clin Endocrinol Metab 2001; 86(8) : 3494-3498.(Zlotkin David, Varma Sure)
Abstract
The treatment of children with short stature was revolutionized by the creation of recombinant growth hormone therapy. While it cannot be denied that therapy adds significant height to children who are growth hormone deficient, such treatment is both painful, requiring many injections for years, as well as extremely expensive, both for the children's parents as well as for medical health care for society. With the indications for growth hormone treatment expanding over the years to include children with short stature who are not growth hormone deficient, it is important to determine all potential benefits beyond the obvious physical effects in order to make efficient cost-benefit determinations on appropriate usage of growth hormone therapy. One aspect of possible benefits for these children with short stature may be psychological features, such as increased overall happiness and self-esteem that is gained with increased height. A review and analysis of literature was undertaken in order to determine what effect, if any, growth hormone therapy has on short children's psychosocial well-being.
Keywords: Short stature; Growth hormone; Psychological
Since the introduction of recombinant growth hormone (GH) therapy in 1985, a vast number of children have undertaken therapy to improve their eventual adult height. With cost of such treatment exceeding $20,000 per year for several years, many third-party payers have shown reluctance in providing such treatment. While it is well established that GH therapy will have a positive effect on height, the impact on psychological factors is less proven. It has been assumed that children of short stature experience behavioral disorders secondary to adverse social experiences and that an increase in height would alleviate these events, resulting in adults that would have greater cognitive functioning than they would have if they were not treated. If this hypothesis was proven to be valid, the overall financial cost of GH therapy would be lessened, both by the reduced amount of psychological services required by these children as well as the increased productivity and contribution to society as higher functioning adults. In order to determine the non-linear effect of GH therapy, a review and analysis of the literature was undertaken.
During the literature review process, many studies were examined in order to validate the hypothesis that GH therapy would have a beneficial effect on the psychological aspects of children. Several early psychological studies of children with short stature showed an increased percentage of problems, including social aversion, anxiety, and attention problems when compared to controls. However, in these studies, children were usually described as 'dwarfs' or 'hypopituitary children', making it difficult to discern if the children studied had isolated GH deficiency (GHD) or suffered from other genetic or medical conditions, which can also contribute to potential psychological problems.[1]
Other studies were performed by surveying adults that were treated for GHD as children and comparing their quality of life measures to the general population. While the GH treated adults were less likely to be married, perform well in school, or gain meaningful employment, the exact clinical psychological impact of these results are difficult to interpret[2] .
Stabler et al[3] compared 195 children of short stature with a control group and measured the prevalence of behavioral and learning problems. The children were further classified as being GHD or idiopathic short stature (ISS) via responsiveness to stimulation testing. Overall, a greater number of short stature children had difficulty in school and suffered from behavioral problems than those of controls. No differences were observed specifically between the GHD group and those of ISS. There were no statistically significant differences in academic achievement observed between the two groups. After three years of GH therapy in both the groups, both showed improvement in an overall psychological functioning as measured by the Total Behavior Problem scale. Those with GHD, however, showed significant improvement in 7 out of the 8 individual factors, as compared to 2 for ISS, with both groups improving in the Anxious/Depressed and Social Problems subscales. These results mirror those performed on GHD adults, who have been described as more socially isolated and less energetic than GH sufficient controls.
In their study, Erling et al[4] compared sixty short stature children using the Visual Analogue Scale for Children (VASC), again separating GHD children from ISS by stimulation testing. The group of children who were GHD had a more negative self-perception of their physical appearance than compared to controls, which was not seen when those with ISS were compared to those of normal stature, perhaps due to the other physical effects of GHD on muscle formation and adipose deposition in tissues. The authors then took the next step of correlating the maximum amount of GH stimulated during testing to the same VASC subscales. The results showed a strong negative correlation between the maximal GH amount of the children and the inhibition subscale, stating that the children that have the least amount of GH were described as being more inhibited by both the children themselves as well as their parents. It has been theorized that since the neuro-endocrine centers that modulate mood and affect are functionally related to GH secretion by the pituitary, that decreased amounts of GH available would have a negative effect on these psychological factors.[5] This theory may explain the lower social skills achieved by GHD adults which have been consistently revealed by other studies[6] .
Van Pareren et al[7] examined children born small for gestational age (SGA) in the Netherlands, treated them with GH, and followed them for two and eight years, obtaining psychological values at baseline as well as each follow-up visit. The children were not divided between GHD and ISS. At baseline, the SGA children showed lower values in performance IQ as compared to population controls. This value improved significantly at two years post-GH therapy and at eight years was at par with the average Dutch samples. This effect was also seen in other areas, such as behavioral problems, which decreased from above the norm at baseline to average values. The most dramatic effect was seen in the mean self-perception scale, where the SGA children showed values well below the mean at baseline, was equivalent at two years post-treatment, and actually exceeded the average at eight years post GH therapy.
Finally, Wiren et al[8] took the next step by following adolescents who had been treated for GHD after their treatments were terminated due to their achievement of total adult height. These young adults were studied over a two year period to determine if the abrupt cessation of GH had a negative psychological effect. The data was further separated into those with GHD and those classified as GH sufficient, which is equivalent to the ISS category. While those with GHD had a decline in sociability and an increase in anxiety, not seen in the ISS group, there was no measurable decline in overall quality of life in either group of subjects. Therefore, any potential psychological gain made during GH therapy does not appear to deteriorate once therapy had ceased.
While the above studies were performed using various methods, the conclusions drawn state that GHD children are at higher risk for social difficulties and anxiety disorders, even greater than those with ISS. With GH therapy through to final adult height, these risks appear to be lessened and remain so through adulthood after GH discontinuation. Whether this is a direct effect of GH on the hypothalamic-pituitary axis or by increased social value associated with greater height is a question for further studies to answer. At the very least, the data shows that there are effects of GH therapy on GHD children that expand beyond the increase in final adult height and these factors should be taken into consideration when they are prescribed for these children.
References
1. Steinhausen H, Stahnke N. Psychendocrinological studies in dwarfed children and adolescents. Arch Dis Child 1976; 51: 778-783.
2. Bjork S, Jonsson B, Westphal O, Levin J-E. Quality of life of adults with growth hormone deficiency: a controlled study. Acta Paediatr Scand 1989; 356 (Suppl): 55-59.
3. Stabler B, Clopper RR, Siegel PT, Stoppani C, Compton PG, Underwood LE. Academic achievement and psychological adjustment in short children. J Dev Behav Pediatr 1994; 15: 1-6.
4. Erling A, Wiklund I, Wikland K. Psychological functioning in boys of short stature: effects of different levels of growth hormone secretion. Acta Paediatr 2002; 91: 966-971.
5. Abelson JL, Glitz D, Cameron OG, Lee MA, Bronzo M, Curtis GC. Blunted growth hormone response to clonidine in patients with generalized anxiety disorder. Arch Gen Psychiatr 1991; 48(2): 157-162.
6. Barker DJ, Erikkson JG, Forsen T, Osmond C. Infant growth and income 50 years later. Arch Dis Child 2005; 90(3): 272-273.
7. van Pareren, YK, Duivenvoorden FS, Slijper FS, Koot HM, Hokken-Koelega AC. Intelligence and psychological functioning during long-term growth hormone therapy in children born small for gestational age. J Clin Endocrinol Metab 2004; 89(11): 5295-5302.
8. Wiren L, Johnannson G, Bengtsson B. A prospective Investigation of quality of life and psychological well-being after the discontinuation of GH treatment in adolescent patients who had GH deficiency during childhood. J Clin Endocrinol Metab 2001; 86(8) : 3494-3498.(Zlotkin David, Varma Sure)