A comparison of traditional approaches to hierarchical linear modeling when analyzing longitudinal data.

Longitudinal designs typically involve repeated time-ordered observations for each individual (or unit). Such designs are uniquely suited to studying changes over time within individuals, and relating these to individual characteristics to identify processes and causes of intra- individual changes and interindividual differences in physiologic and psychological development. The purpose of this paper is to compare and contrast univariate and multivariate ANOVA with repeated measures to hierarchical linear modeling as approaches to analyzing such longitudinal data. This will enable researchers to choose the approach that best meets their research needs, and it will enable them to compare research results that are reported using one analytical approach with results that are reported using the other approach.

Behavior change after growth hormone treatment of children with short stature.

OBJECTIVES: To measure the prevalence of behavioral and learning problems among children with short stature and to assess the effect of growth hormone (GH) treatment on such problems. STUDY DESIGN: A total of 195 children with short stature (age range 5 to 16 years, mean age 11.2 years) were tested for intelligence, academic achievement, social competence, and behavior problems before beginning GH therapy and yearly during 3 years of treatment. Children were classified as having growth hormone deficiency (GHD) when GH responses to provocative stimuli were <10 ng/mL (n = 109) and as having idiopathic short stature (ISS) when >10 ng/mL (n = 86). A normal-statured matched comparison group was tested at the baseline only. RESULTS: Seventy-two children in the GHD group and 59 children in the ISS group completed 3 years of GH therapy and psychometric testing. Mean IQs of the children with short stature were near average. IQs and achievement scores did not change with GH therapy. Child Behavior Checklist scores for total behavior problems were higher (P < .001) in the children with short stature than in the normal-statured children. After 3 years of GH therapy these scores were improved in patients with GHD (P < .001) and ISS (P < .003). Also, there was improvement in the scores of children in the GHD group in the internalizing subscales (withdrawn: P < .007; somatic complications, P < .001; anxious/depressed, P < .001) and on the 3 components of the ungrouped subscales (attention, social problems, and thought problems, each P = .001). Larger effects were observed in the GHD group than in the ISS group. CONCLUSIONS: Many referred children with short stature have problems in behavior, some of which ameliorate during treatment with GH.

Current dosing of growth hormone in children with growth hormone deficiency: how physiologic?

The current doses of recombinant growth hormone (rGH) are two to three times those used in the pituitary growth hormone era. These rGH doses (0.025 to 0.043 mg/kg/d) are similar to or moderately greater than the physiologic requirements. Growth velocity and height gains have been shown to be greater with 0.05 mg/kg/d of rGH than with 0.025 mg/kg/d. Larger doses of GH and early initiation of treatment result in greater heights at the onset of puberty and greater adult heights. Earlier onset of puberty and more rapid maturation, as indicated by bone age, were not observed in children who were given 0.18 to 0.3 mg/kg/wk of rGH. The frequency of adverse events is very low, but diligent surveillance of all children who are treated with rGH is essential.

Quality of life among formerly treated childhood-onset growth hormone-deficient adults: a comparison with unaffected siblings.

Several studies have investigated the quality of life (QOL) of GH-deficient (GHD) adults who, as children, had been treated with GH. Variable findings are probably related to sample heterogeneity and disparate research methodologies and designs, particularly the choice of control or comparison groups. In addition to comparing a relatively large sample to questionnaire norms, the present study is the first to compare the QOL adjustment of GHD patients to that of same sex siblings. A total of 140 former patients (76% of those eligible; mean age, 26 yr; n = 95 isolated GHD, n = 45 multiple pituitary hormone deficiencies; 117 males and 23 females) and 53 same sex siblings (84% participation), 18 yr and older, participated in the telephone questionnaire survey. The majority of interviews with GHD patients (78%) and siblings (87%) were conducted blind to the subject's clinical status. Comparisons between GHD patients and norms for standardized questionnaires indicated both better and worse functioning in several domains. In contrast, very limited differences were detected between GHD cases and same sex siblings. Isolated GHD patients were functioning better than those with multiple pituitary hormone deficiencies, but the effect sizes of these differences in most areas were relatively small. Adult height and degree of growth over the course of GH therapy were generally unrelated to QOL outcomes. Findings from the present study underscore the importance of selecting unbiased control/comparison groups in evaluating psychological outcomes among GHD adults.

Links between growth hormone deficiency, adaptation and social phobia.

Children referred for growth hormone (GH) treatment have increased school achievement problems, lack appropriate social skills and show several forms of behavior problems. A multicenter study in the United States has revealed that many GH-impaired children exhibit a cluster of behavioral symptoms involving disorders of mood and attention. Anxiety, depression, somatic complaints and attention deficits have been identified. These symptoms decline in frequency over a period of 3 years, beginning shortly after GH replacement therapy is started. Many of the patients who have received GH and had good growth responses show lower than average quality of life in young adulthood after treatment is completed. GH-deficient adults placed on GH therapy report improvement in psychological well-being and health status, suggesting that GH might have a central neuroendocrine action. Among a group of adults who were GH deficient as children, we find a high incidence of social phobia, a psychiatric disorder linked to GH secretion and usually accompanied by poor life quality. An ongoing study of non-GH-deficient short individuals suggests that short stature is not the cause of this outcome. We conclude that the origins of psychiatric comorbidities, such as social phobia and depression, in GH deficient adults are likely to be neuroendocrine as well as psychosocial.

Academic achievement and psychological adjustment in short children. The National Cooperative Growth Study.

Limited information is available on the educational and behavioral functioning of short children. Through 27 participating medical centers, we administered a battery of psychologic tests to 166 children referred for growth hormone (GH) treatment (5 to 16 years) who were below the third percentile for height (mean height = -2.7 SD). The sample consisted of 86 children with isolated growth-hormone deficiency (GHD) and 80 children with idiopathic short stature (ISS). Despite average intelligence, absence of significant family dysfunction, and advantaged social background, a large number of children had academic underachievement. Both groups showed significant discrepancy (p < .01) between IQ and achievement scores in reading (6%), spelling (10%), and arithmetic (13%) and a higher-than-expected rate of behavior problems (GHD, 12%, p < .0001; ISS, 10%, p < .0001). Behavior problems included elevated rates of internalizing behavior (e.g., anxiety, somatic complaints) and externalizing behavior (e.g., impulsive, distractable, attention-seeking). Social competence was reduced in school-related activities for GHD patients (6%, p < .03). The high frequency of underachievement, behavior problems, and reduced social competency in these children suggests that short stature itself may predispose them to some of their difficulties. Alternately, parents of short, underachieving children may be more likely to seek help. In addition, some problems may be caused by factors related to specific diagnoses.

Psychosexual behavior in hypopituitary men: a controlled comparison of gonadotropin and testosterone replacement.

Nine gonadotropin-deficient hypopituitary men were cycled through periods of treatment with testosterone (T), gonadotropin (Gn), and placebo (Pl) using a blind cross-over design. Self-reports of sexual behavior, recordings of nocturnal penile tumescence (NPT), and sex steroid levels were obtained during each treatment period. Subjects had significantly higher plasma T during the T and Gn treatments than during the control periods. Similarly, self-reported frequency of ejaculation and ratings of libido as well as duration measures of NPT were significantly higher on T and Gn. Two thirds of the sample had no sociosexual experience. Behavioral differences between the T and Gn periods were minimal. These data support the hypothesis that Gn and T are equally effective in stimulating specific aspects of male psychosexual behavior.

Pubertal disorders. Psychology and clinical management.

The behavioral data reviewed herein must be viewed with caution. Although there are reports that adhere to rigorous methodology, these are the exception. Most reports do not adequately describe either the methodology used or their sample. Subjects are often of mixed endocrine diagnoses, and sometimes the results are of both boys and girls. All of these pitfalls make interpretation of results difficult and limiting. With this in mind, the following conclusions are offered. The majority of behavioral data on precocious puberty comes from studies of IPP in girls. Cognitively, IPP has been associated with average to high-average intelligence. Purportedly, the finding of lower visual-spatial skills than verbal skills in early maturing boys and girls has received equivocal support by cognitive studies of IPP individuals. Similarly, clear differences in hemispheric lateralization have not been demonstrated. Aside from increased somatic complaints during the nonmenstrual phases of their menstrual cycle, girls with IPP show a spectrum of behavior adjustments. Major psychopathology is rare. Clearly, their early development makes them look older than their actual age, which probably alters the expectations others have for them. Psychosexually, however, IPP girls develop in concert with their chronologic age and social experience, rather than their early biologic maturation. However, recent reports suggest a modest influence of hormones. In summary, these studies support an interactionist theory of human psychosexual development. Research data on IPP girls suggest that they do not significantly differ from girls who are early maturers but within the normal range. Research on these girls indicates that most negotiate their puberty without severe problems. There has been less research on IPP boys because it occurs so rarely. Most of what is understood about precocious puberty in boys comes from boys with precocious puberty secondary to poorly controlled CAH. Behavioral data on individuals with delayed puberty come almost exclusively from boys. Although CD appears to be the most frequently diagnosed form of delayed puberty and does not reflect a known pathologic process, men with CD as well as those with organic disorders appear to be at risk for psychosocial and psychosexual difficulties. These difficulties are not severe forms of psychopathology. Rather, they probably represent problems negotiating the expected adolescent lessons of psychosocial development with a physique that places them at a disadvantage. They clearly look younger than their actual chronologic age. Cognitively, as with the children with precocious puberty, there is no evidence of intellectual impairment associated with delayed puberty.(ABSTRACT TRUNCATED AT 400 WORDS)

Growth hormone deficiency in children has psychological and educational co-morbidity.

Growth delay caused by growth hormone deficiency (GHD) is a condition presented with increased frequency to pediatricians. Recent evidence suggests these patients should be evaluated developmentally for behavioral and educational problems. Such assessment would assure a comprehensive approach to treatment and increase the likelihood of a satisfactory outcome in young adulthood. This article briefly reviews what is known about the behavioral and educational difficulties experienced by growth hormone deficient patients. Specific recommendations for educational assessment and anticipatory guidance are presented.

Data on virilization and erotosexual behavior in male hypogonadotropic hypopituitarism during gonadotropin and androgen treatment.

The goal of this investigation was to assess whether or not gonadotropin therapy enhanced the degree of virilization and psychosexual behavior of men with hypogonadotropic hypopituitarism. Pre- and post-gonadotropin assessments of virilization in four men indicated that gonadotropin therapy was associated with dramatic improvements in the degree of virilization that each man previously obtained on androgen only. Retrospective interview data on erotosexual behavior indicated improved erotosexual function on gonadotropin as compared to the prior androgen treatment. These data suggest that complete virilization in these men was partially gonadotropin dependent. Whether or not the behavioral benefits reported by these men represented a direct or synergistic effect of gonadotropin in the expression of erotosexual behavior or an indirect effect of improved virilization can not be answered by these data.