Psychosocial Correlates of Short Stature and Delayed Puberty

Psychosocial Correlates of Short Stature and Delayed Puberty

Pediatric and Adolescent Endocrinology 0031-3955/87 $0.00 + .20 Psychosocial Correlates of Short Stature and Delayed Puberty Phillip D. K. Lee, MD...

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0031-3955/87 $0.00

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Psychosocial Correlates of Short Stature and Delayed Puberty

Phillip D. K. Lee, MD,* and Ron C. Rosenfeld, MDt

Research interest in the relationship between growth retardation and psychological dysfunction dates back over 30 years. Initial case reports interpreted in the light of psychoanalytic theory indicated that short stature was associated with a variety of psychopathology. Subsequent studies gave conflicting results but seemed to indicate that growth retardation could be associated with lower intelligence and an increased incidence of psychologic problems. With the advent of growth hormone therapy, interest revolved around the possible effects of growth stimulation on psychological symptoms. In general, improvements in growth rate and final adult height seemed to have little effect on psychosocial adjustment, and in some cases appeared to be detrimental. The recent increased availability of growth hormone and the prospect of its use in non-growth hormone deficient short children has given new importance to the interrelationships of growth retardation, psychosocial and intellectual dysfunction, and the effects of hormonal therapy. The consideration of psychosocial factors should play a key role in the treatment of short stature.

DEFINITIONS In most investigations, short stature is defined as height greater than two standard deviations below the mean height for chronologic age. Short stature is a characteristic rather than a diagnosis and is associated with normal variation, chronic disease, hormonal and nutritional disorders, as well as a wide variety of dysmorphic syndromes. In this review, we will primarily address the psychosocial issues related to three diagnostic cate*Assistant Professor of Pediatrics, The University of Colorado Health Sciences Center, Division of Pediatric Endocrinology, The Children's Hospital, Denver, Colorado t Associate Professor of Pediatrics, Division of Pediatric Endocrinology and Metabolism, Department of Pediatrics, Stanford University, Stanford, California

Pediatric Clinics of North America-Vol. 34, No.4, August 1987

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gories: (1) hypopituitarism, including all cases of documented growth hormone deficiency whether idiopathic or due to pituitary pathology; (2) constitutional delay of growth, in which a delayed rate of development relative to the norm leads to childhood short stature and delayed puberty, but a normal final adult height; and (3) familial or normal variant short stature, in which the rate of physical development is normal and short stature as a child and adult is consistent with the genetic background. 2, 46

SHORT STATURE AND INTELLIGENCE Few subjects have engendered as much controversy as human intelligence and the factors which may affect it. The possibility that growth retardation and intelligence might be related was first formally addressed by Martin and Wilkins,31 who found a normal distribution of intelligence quotient (IQ) scores for 12 children with growth hormone deficiency. Pollitt and Money44 studied 15 children before initiation of growth hormone therapy and found no association of stature and intelligence, with average IQ scores in the normal range. Subsequent studies in a variety of pat~ent populations, including constitutional and familial short stature, Turner's syndrome, and hypopituitarism, have similarly failed to demonstrate an independent relationship between short stature and intelligence. 1, 10,33,40,58, 63 Some studies have shown lower IQ scores in children with deprivational dwarfism,lO intrauterine growth retardation,26 and hypopituitarism, however. 1, 16 Although these studies indicate that short stature and lower intelligence are not necessarily correlated, the data are limited by small sample sizes, lack of appropriate control groups, and possible bias in the patient sample selection. Moreover, because of the small sample sizes, these investigations are unable to address the question of whether degrees of short stature vary directly with IQ scores. Data from several population studies have been analyzed with regard to this controversial issue. In a longitudinal follow up of 6912 Scottish children born in 1936,53 a relationship was found between height and intelligence, with an average correlation coefficient of 0.25. Test scores showed a similar variation with several environmental factors, including family and household size and occupational class, leading the authors to conjecture that height and test scores vary independently with a common environmental influence. Similar longitudinal data on 5362 British children born in 19469 showed a significant correlation of approximately 0.15 between height and intelligence at ages 7 and 8 years, 11 years, and 15 years. This correlation was observed even when the data were controlled for sex, age, pubertal stage, social class, and family size. Miller et al. 34 reported data from a longitudinal study initially involving 1141 children born in 1947, of which 763 were remaining at age 15 years. Significant correlations were found between heights at 3 and 5 years of age and intelligence at 11 or 12 years of age, although the data were not adjusted for other factors which were also shown to influence IQ scores, such as maternal age, birthrank, and social background. Interestingly, the

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IQ scores showed no correlation with birthweight, suggesting that the influence of height on IQ scores may be more directly related to the postnatal growth rate. Recently, Wilson et al. 62 analyzed data on 7119 children aged 6 to 11 years from cycle II (1963-1965) and 6768 children aged 12 to 17 years from cycle III (1966-1970) of the U.S. National Health Examination Survey.43 A highly significant correlation (average coefficient 0.2, p95th percentiles for height, although average scores for all height groups were within the normal range. Overall, data from these population studies indicate that children with short stature have normal intelligence, although tending to score lower than their peers on standardized tests. The significance of this observation remains to be determined; however, these data clearly cannot be used to infer assumptions about the individual child with short stature. The statistical correlations between height and IQ are small and account for about 1 to 5 per cent of the total variance in IQ.lO, 62 Such results may be explained by the independent correlations of height and IQ with other unmeasured parameters. PSYCHOLOGICAL CHARACTERISTICS

Numerous publications have addressed the question of whether short stature is associated with an increased incidence of psychopathology. Green et al. 22 presented an in-depth psychoanalysis of a lO-year-old child with growth retardation in association with severe deficits in emotional development, including lack of aggressive drive and abnormal object relationships. A similar lack of aggressiveness was found in six children with hypopituitarism, but not in a control group of six children with constitutional or genetic short stature. 28 Children with hypopituitarism also have been found to differ from those with constitutional delay of growth in terms of a number of factors, including morphologic characteristics, socioeconomic background, and birth history6o; these factors may ~t least partially account for the differences in psychological characteristics. The importance of distinguishing subgroups of children with short stature was further emphasized by Drash et al. ,10 who studied patients with four different diagnoses: hypopituitarism, Turner's syndrome, achondroplasia, and deprivational dwarfism. The 36 subjects with hypopituitarism, who were described in more detail in a separate publication,40 showed a marked delay in psychological maturation and a lack of aggressive drive. In contrast, the patients with Turner's syndrome had essentially normal personality adjustment, the achondroplasts were described as outgoing, cheerful, and optimistic, and the children with deprivation dwarfism displayed bizarre,

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aggressive, and uncontrollable behavior. 42 Unfortunately, children with constitutional short stature were not included in this study. Possible deficiencies in self-image and aggressiveness in association with short stature have been studied by several investigators. A positive self-image was found in a control group but not in 64 children with various forms of short stature (not including constitutional short stature). 17 Rotnem et al. 49 studied 14 children with hypopituitary short stature and found significant deficits in self-image, including feelings of social isolation, powerlessness, incompetence, and low self-esteem. An inability to express aggression was also characteristic. Spencer and Raft,55 using three illustrative case reports, pointed out that it is the expression of aggression, and not the aggressive drive itself that is apparently impaired in hypopituitary persons. Drotar et al. 11 confirmed a lack of expression of aggression in 16 children with short stature secondary to hypopituitarism but were unable to detect any deficits in body image, sex role development, or general psychological adjustment when compared to a control group. Using human figure drawing tests, Money et al. 39 showed that short children have a tendency to miniaturize depictions of themselves and others, but otherwise showed no evidence of impaired body image or sexual identity. No differences in anxiety levels and locus of control were found in 36 children with hypopituitarism, as compared to an age-matched control group consisting of children with chronic nonfatal illnesses. 56 The same investigators studied 28 hypopituitary and 3 non-growth hormone deficient boys with short stature using the Wechsler picture arrangement subtest and found that although measures of social judgment are impaired, responses to competitive stress were comparable to an age-matched normalstature control group. 57 These data were interpreted as reflecting relative social immaturity and support previous data relating short stature and social immaturity,30 but also suggest normal responses to competitive tasks. The same test administered to a group of20 children with constitutional delay revealed no abnormalities in relation to a control group with normal stature. 21 Response to competitive stress was not investigated. Children with constitutional short stature also showed no evidence of psychopathology in comparison to a matched control population, although shyness, impaired self-concept, and social withdrawal were noted. 20 In summary, it appears that there is no conclusive evidence that short stature per se is associated with psychopathology. Certain personality characteristics are consistently found in association with specific diagnoses, however. In particular, children with short stature secondary to hypopituitarism display a relative inability to express their aggressive drives and tend to be more socially withdrawn than their peers. Whether this represents psychological disturbance or a nonpathologic adaptive mechanism remains to be determined. Furthermore, impairment in peer relationships or social interactions as a result of these personality traits has yet to be demonstrated. ACADEMIC PERFORMANCE We turn now from what might be considered personal characteristics, namely, intelligence and personality, to a discussion of the ability of short

1

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children to function in their environment, specifically in terms of academic performance and long-term psychosocial adjustment. Because children spend most of their out-of-home time in school, academic performance provides an important measure of psychosocial adjustment in childhood. Relatively few studies, however, have addressed the relationship between height and academic performance. Investigations of school performance in hypopituitary children with short stature have given conflicting results. Fifteen growth hormone deficient children studied prior to therapy were found to have impaired academic performance, which was unrelated to scores on intelligence testing. 44 Similarly, parental assessment of school performance in 17 hypopituitary children, using the Achenbach Child Behavior Checklist, revealed significant deficits, particularly for the female children studied. 27 Twentytwo of forty-two (52 per cent) hypopituitary children were found to be low academic achievers. 54 Furthermore, in this study, low achievement was shown to correlate with decreased cognitive ability. In contrast, Rosenbloom et al. 45 found satisfactory academic achievement in 9 of 10 children with hypopituitarism. Differences between the two studies were attributed to possible differences in social support systems, although the small sample sizes and selection bias in both studies were probably of at least equal importance. Studies in non-growth hormone deficient populations have likewise given conflicting results. A small study in West Germany showed that 6 of 10 children with nonorganic short stature were delayed in grade level, as compared to 2 of 7 with hypopituitarism. 59 Gold 19 found significant differences in academic performance between children with constitutional delay of growth and familial short stature in Nassau county, Florida. Learning problems were reported for 171 of 591 (29 per cent) children with constitutional delay, as opposed to 19 of 435 (4 per cent) children with familial short stature. In addition, minimal cerebral dysfunction was diagnosed in 21 of the former and none of the latter group. These results suggested that the developmental delay associated with constitutional short stature may lead to im~ aired learning ability. Conversely, Gordon et al. 21 studied 20 children with constitutional delay in relation to controls with normal stature matched for age, sex, and socioeconomic status and were unable to demonstrate differences in 15 separate measures of intellectual, visual-motor, and academic function. The authors attributed the apparent increased incidence of learning disorders in the previous study to lack of an appropriate normal control group. Differences in the study populations and the parameters under observation may also account for some of the discrepancies. Thus, it appears that the question of underachievement in relation to short stature remains unresolved, and there is no conclusive evidence that short stature per se is associated with impaired school performance. School performance and social functioning for children with short stature depend primarily on family attitudes and support systems 63 and attention to these factors may prove beneficial in selected cases.

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LONG-TERM PSYCHOSOCIAL ADJUSTMENT

What happens to the short child who becomes a short adult? From the data thus far presented, there appears to be no consistent reason to expect that short persons will have deficits in social adaptation. As reviewed by Gillis, however, numerous studies have shown that there is a direct correlation between height and various measures of social success, such as income and occupational status. 18 Schumache~o investigated several occupations and found that individuals in higher ranking positions were statistically taller than their colleagues, even when the data were controlled for social and educational background. Possible reasons for this finding were suggested in an accompanying study51 in which it was found that vocational trainees perceived that both tall and successful people share personality characteristics, but that short persons do not share the characteristics of successful people. The importance of societal conditioning is further indicated by studies such as that by Caplan and Goldman,4 showing that adults are less likely to violate the personal space of a tall as opposed to a short person in a crowded train station. In addition to these findings relating to occupational status, several reports have detailed deficits in adult social behavior and emotional relationships. For instance, in a series of studies involving hypopituitary male subjects with and without hypogonadotropinism,5, 37, 38 decreased frequencies of sexual activity and pair bonding were observed that were not readily explained by deficits in sexual development. Similar data were reported for adults with short stature in association with skeletal dysplasia, in which only one third were married, as compared to over three quarters of both the general U. S. population and a subgroup of disabled persons without short stature. 15, 61 Brust et al. 3 reported slightly better results in a population of 16 hypopituitary and achondroplastic dwarfs, of whom 8 were married. The hope that growth hormone therapy and the resultant increase in height might lead to improvements in social adjustment has apparently not been fulfilled. Kusalic et al. 30 reported that 1 year of growth hormone therapy led to unrealistic expectations with respect to height, as well as evolution of the preexisting low self-esteem into a depressive affect, and a partial release of aggressive drives in 11 hypopituitary children. Mter 5 years of therapy, psychological disturbances intensified in the older patients, with some developing signs of psychosis. 29 Interestingly, the younger patients showed superior psychological adjustment, suggesting that previous psychosocial conditioning may be an important influence. No relationship between height gain and psychological symptoms was found. Similar results were obtained in a sample of 11 hypopituitary children treated with growth hormone. 48 After 1 year of therapy, many of the children experienced accentuation of their poor self-concept. In addition, despite a positive growth response, expectations of therapy for both parents and patients were apparently not met, leading to disappointment, grief, and anger in several children. The relatively good psychosocial adjustment observed for the younger patients was attributed to their better growth response to therapy. The importance of considering parental and patient expectations is supported further by the findings of a high rate of overesti-

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mation of current and predicted height among 14 children being treated for growth hormone deficiency and among their parents. 23 In contrast to these studies, longitudinal follow up of 17 hypopituitary children treated with growth hormone failed to demonstrate appearance of either aggressive or psychotic behavior, although other less severe difficulties in adjusting to the increased growth rate were noted. 41 Siegel and Hopwood54 administered the Piers-Harris Self-Concept Inventory to 38 hypopituitary children receiving growth hormone replacement therapy and were unable to detect deficits in self-esteem as compared to normative standards. Pretreatment data regarding self-concept were not available, however. Three follow-up studies of growth hormone deficient adults previously treated with growth hormone have given us additional insight into this area. Dean et al. 7 located 116 growth hormone deficient persons in Canada who had received at least 2 years of replacement therapy between 1967 and 1982. Although educational achievement was comparable to both sibling controls and the general population, unemployment rates were twice as high as in the general population, even when controlled for age. In addition, only 15 of the subjects were married, representing less than 30 per cent of the expected age-adjusted rate. No difference in outcome was noted between the patients with isolated growth hormone deficiency and organic hypopituitarism. Thus, despite a positive response to growth hormone therapy, patients failed to show normal psychosocial adjustment. Almost identical results were found in a follow up of 58 growth hormone deficient patients treated at Johns Hopkins University and the University of Virginia. 35 Although educational attainment was similar to sibling controls, unemployment was twice that for the general population. Furthermore, significant impairments in self-concept and peer relationships were noted. Interestingly, 64 per cent indicated that their initial expectations for therapeutic outcome were met, and an additional 32 per cent felt that they were partially met. Thus, the deficits in psychosocial adjustment persisted even with attainment of an expected therapeutic outcome. More optimistic results were reported by Clopper et al. 6 for 39 young adults previously treated for growth hormone deficiency. All but two patients completed high school, 70 per cent continued their education, and only three subjects were unemployed and not attending school. On the other hand, delayed separation from the parental home was noted, and only 4 of these people were married. Overall, the long-term prognosis for good psychosocial adjustment is relatively poor for children with short stature secondary to hypopituitarism, and there is no evidence that it is improved significantly with growth hormone therapy. Whether this is due to the fact that most children with growth hormone deficiency have in the past not attained normal adult height with therapy should be investigated since the increased availability of growth hormone allows more liberal replacement. Judicious use of counseling and psychological therapy and involvement in organizational support groups also may be useful therapeutic adjuncts in individual cases, 13. 23. 25, 32, 36, 52, 61 although there is no current evidence that this improves outcome.

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Psychosocial outcome for the more common familial or normal variant form of short stature remains less well defined. Although statistical correlations between social success and height can be demonstrated, it might be expected that most patients in this group have good psychosocial adjustment because adjustment during childhood appears to be relatively normal. Clearly, more definitive data relating to this population will be useful in the near future as the widespread treatment of normal variant short stature with growth hormone becomes a possibility.

DELAYED PUBERTAL DEVELOPMENT Normal age of onset for pubertal development follows a modal distribution. By convention, delayed puberty is defined as greater than two standard deviations retardation relative to the mean; corresponding to approximately 12 to 13 years of age for girls and 14 to 15 years for boys. 2, 46 In this section, we will review data relating to the psychological consequences of constitutional delay of puberty, which is the most common etiology of pubertal delay. The psychosocial effects of pubertal failure secondary to organic causes is a more complex problem by nature of its permanence and the need for long-term therapy; this topic has recently been reviewed. 13, 14 Many of the psychosocial factors previously discussed for constitutional delay of growth are also applicable to constitutional delay of puberty. This is not suprising since the two conditions are usually coexistent, and very few studies have attempted to factor out their individual influences on . psychosocial functioning. Both prospective and retrospective studies published over the past 40 years show that late maturation in boys is associated with poor self-concept, feelings of inadequacy, underdeveloped social interactions, and lack of independence. In addition, these traits and their consequences appear to persist into adulthood despite attainment of normal height and development. 14, 24 Sexual maturation has also been shown to have an independent correlation with measures of intellectual ability among 2864 children in the British National Survey.9 Galatzer et al. 17 studied 37 boys and 22 girls with delayed puberty with or without short stature. Scores on the Tennessee Self-Concept Scale were low as compared to a control group, indicating poor self identity. The relatively poor self-concept correlated well with delayed sexual development but not with stature, suggesting that the former may be the more important contributory factor. Data from Cycle III of the U. S. National Health Examination Survey conducted during the period from 1966 to 197043 and involving detailed examinations of a random population of over 6700 12 to 17-year-old subjects are also relevant to this issue. Heterosexual dating behavior for both sexes was found to correlate significantly with both chronological age and sexual maturity.8 However, regression analysis and analysis by partial correlations revealed that age was the primary influential factor, with sexual maturity

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contributing very little to the observed variance, implying that peer and other social pressures may be more important than sexual maturation in determining dating behavior. Among the male adolescents, late maturity was correlated with poor ratings on eight education-related variables, including measures of parental and self-aspirations and expectations, teacher reports, and scores on intelligence and achievement tests. 12 These interrelationships were not found among the female adolescents. Hormonal therapy of constitutional pubertal delay is a controversial topic. After excluding organic causes for the delay, most cases can be managed with reassurance and counseling, emphasizing the expected normal outcome for both height and development. In some cases, however, concerns regarding social and academic maladjustment may indicate a need for hormonal intervention. Treatment of delayed puberty in boys with short courses of either oral or intramuscular anabolic steroids has proven effective in stimulating short term growth and pubertal development46 , 58 and may also result in maturation of the hypothalamopituitary-gonadal axis. Rosenfeld et alY treated eight boys with constitutional delay of puberty with 4 intramuscular injections of testosterone enanthate (200 mg per dose) given 3 weeks apart. Subjects in the study were preselected as having significant psychosocial difficulties secondary to their delayed development. Definite improvements in growth rate and sexual maturation were noted as compared with a control group assigned to observation. No adverse side effects occurred, and bone age advancement remained appropriate, indicating no compromise in adult height. Although both groups showed improved self-concept at I-year follow up, social activity was improved in the treated boys relative to the controls. On the basis of these results and our subsequent experience with this treatment protocol, we recommend that this therapy be considered in selected cases in which the pubertal delay is causing significant psychosocial maladjustment. Constitutional delay of puberty in girls is, in our experience, a very uncommon presenting complaint. The reasons for this are uncertain, but may be related to sexual differences in modes of social adaptation and in the relative frequencies of organic etiologies for pubertal delay. As discussed above, delayed development in girls does not show the same degree of negative variance with academic achievement as is observed with boys. Hormonal intervention for constitutional delay of puberty in girls is rarely indicated, and specific protocols remain unproven.

CONCLUSIONS Short stature has been linked to a variety of psychological and intellectual variables that should be taken into account when considering therapeutic intervention. Unfortunately, data relating to these variables have been largely inconclusive. Shorter persons tend to score lower in tests of intelligence; however, functionally significant deficits in intelligence have not been definitely associated with short stature per se. Short stature also

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appears to bear no particular relationship to any form of childhood psychopathology, although personality traits such as introversion and internalization of aggressive drives have been associated with hypopituitarism. Studies relating to academic performance have likewise proved to be difficult to interpret, with reports of both normal and under achievement in children with short stature. In contrast to these results relating to childhood psychosocial functioning, hypopituitary short stature in adulthood is associated with poor adjustment, including low rates of employment and impaired social relationships. This may in part be due to the generally negative societal attitudes toward short persons. Moreover, growth hormone therapy has thus far proven to be relatively ineffective in improving the psychosocial outcome for hypopituitary patients. Physicians and other health professionals who care for children with short stature need to maintain an awareness of possible difficulties in psychosocial adjustment. In selected cases, psychological counseling and organizational support groups may be of benefit. It remains to be determined whether the increased availability of growth hormone, and the resultant increased potential for height normalization in hypopituitary children, will prove beneficial in terms of long-term psychosocial adjustment. These issues also will need to be addressed with regard to treatment of children with normal variant short stature. Studies of delayed puberty associated with constitutional delay of growth indicate an association of pubertal delay with poor self-image and social immaturity. Recent studies suggest that the poor self-concept in constitutional delay may be more strongly related to sexual maturity than height. However, heterosexual dating behavior is independently correlated with chronologic age but not sexual maturity. Poor academic performance is associated with delayed maturation in boys but not in girls. All of these data indicate the importance of peer and social pressures as determinants of psychosocial adjustment in adolescence. Since a normal outcome for final height and sexual development is expected, most cases of constitutional delay of puberty can be successfully managed with counseling and reassurance. However, for selected cases of delayed puberty in boys, a short course of anabolic steroids can have a beneficial effect on rate of development and social functioning.

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