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The diagnostic term, idiopathic short stature, has emerged over the past 30 years and refers to children with short stature of unknown etiology. Controversy exists regarding the scope of the diagnosis and options for its treatment. This article reviews origins of the diagnosis idiopathic short stature and current diagnostic criteria, scientific advances in delineating etiologies of idiopathic short stature, management options, and implications of management decisions for child health.

Context: Use of growth hormone (GH) therapy to promote growth in children with idiopathic short stature is controversial. A fundamental issue underlying the controversy is uncertainty about the magnitude of effectiveness of GH for this condition., Objective: To determine the effect of GH on short- and long-term growth in idiopathic short stature., Study Design: Systematic review of controlled and uncontrolled studies., Data Sources: MEDLINE (1985-2000), key journals, cross-referencing of bibliographies, abstract booklets, and experts., Study Selection and Data Extraction: We performed a meta-analysis of all studies satisfying the inclusion criteria for idiopathic short stature: initial height below the 10th percentile, normal stimulated GH levels (>10 microg/L), absence of comorbid conditions, no previous GH therapy, treatment with biosynthetic GH, and inclusion of major outcome measures., Primary Outcome Measures: Growth velocity and height SD score (number of SDs from mean height for age and sex) at baseline and after 1 year to evaluate the short-term effect of GH. Adult height was analyzed to evaluate the long-term effect of GH., Data Synthesis: Ten controlled trials (434 patients) and 28 uncontrolled trials (655 patients) met the inclusion criteria. While baseline growth velocities were equivalent at baseline, 1-year growth velocity of the GH-treated group significantly exceeded that of controls by 2.86 cm/y. Similarly, in uncontrolled trials, growth velocity increased after 1 year, and height SD score increased from -2.72 at baseline to -2.19. In controlled studies, the adult height of the GH-treated group significantly exceeded controls by 0.84 SD, and in uncontrolled trials the adult height attained after GH treatment (-1.62 SDs) exceeded that predicted at baseline (-2.18 SDs). These results suggest an average gain in adult height of approximately 4 to 6 cm (range, 2.3-8.7 cm) with GH therapy. Given current treatment costs, this corresponds to more than $35 000 per inch (2.54 cm) gained in adult height in idiopathic short stature., Conclusions: Treatment with GH results in short-term increases in growth for children with idiopathic short stature, and long-term GH can increase adult height. These results are fundamental to decisions about GH use and raise questions about the goals of treatment. Use of GH for idiopathic short stature in clinical practice will depend on its efficacy in promoting growth and the value of this effect to families, physicians, and third-party payers.

Context: There is concern in both the medical community and the general public about mechanisms of medical decision making and the interplay of physician and insurer decisions in determining access to care., Objective: To examine the medical process influencing access to growth hormone (GH) therapy for childhood short stature by comparing coverage policies of US insurers with the treatment recommendations of US physicians., Design and Participants: Independent national representative surveys were mailed to insurers (private, Blue Cross/Blue Shield, health maintenance organizations, programs for Children with Special Health Care Needs, and Medicaid programs, n=113), primary care physicians (n=1504), and pediatric endocrinologists (n=534) with response rates of 75%, 60%, and 81%, respectively. Each survey included identical case scenarios. Primary care physicians were asked decisions about referrals to pediatric endocrinologists. Endocrinologists were asked GH treatment recommendations. Insurers were asked coverage decisions for GH therapy., Main Outcome Measures: Insurer coverage decisions for GH in specific case scenarios were compared with the recommendations of primary care physicians and pediatric endocrinologists., Results: Physician recommendations and insurance coverage decisions differed strikingly. For example, while 96% of pediatric endocrinologists recommended GH therapy for children with Turner syndrome, insurer policies covered GH therapy for only 52% of these children. Overall, referral and treatment decisions by physicians resulted in recommendations for GH therapy in 78% of children with GH deficiency, Turner syndrome, or renal failure; of those recommended for treatment, 28% were denied coverage by insurers. Similarly, GH therapy would be recommended by physicians for only 9% of children with idiopathic short stature, but insurers would not cover GH for the vast majority of these children. Furthermore, the data indicated considerable variation among insurers regarding coverage policies for GH (P<.01)., Conclusions: Access to GH therapy differs depending on the type of insurance coverage. The deep discord between physician recommendations and insurance coverage decisions, exemplified by these findings, represents a major challenge to mechanisms of health care decision making, access, and costs.

Objective: To assess the psychosocial functioning of adults who were evaluated as children for short stature and were not treated with human growth hormone., Design: Inception cohort study., Setting: Hospital-based pediatric endocrinology clinic., Participants: From 1975 to 1980, medical record review indicated that 181 of the children referred to our clinic for concerns about short stature were non-growth hormone deficient. In 1992 and 1993, we were able to recruit 35 of these patients for a follow-up study. Eligible subjects were at least 18 years of age at the time of follow-up., Main Outcome Measures: Standardized self-report questionnaires assessed various domains of psychosocial adjustment. Also, a brief test of intellectual functioning was administered and subjects underwent a semistructured in-person interview to evaluate pragmatic functioning and experiences associated with short stature., Results: Few significant differences between the study sample and standardization samples were found on measures of psychosocial and intellectual functioning. Within-group childhood height during the first evaluation appointment was not significantly associated with most adult measures of psychosocial adjustment. Shorter adult stature was significantly associated with lower educational achievement, lower self-esteem, and greater emotional distress., Conclusions: The absence of significant psychosocial distress or impairment in these subjects brings into question one basis for hormonal treatment for non-growth hormone deficient short stature; that short stature in childhood is likely to lead to psychological dysfunction in adulthood. The results, however, also suggest that shorter stature in adulthood may constitute a psychosocial stressor, increasing vulnerability across several domains.

Objective: To determine current expert opinion and recommendations regarding the controversial issue of the use of growth hormone (GH) to treat short children who do not have classical GH deficiency (non-GHD children)., Study Design: Analysis of a national survey mailed to 534 US physician experts on the management of short stature (pediatric endocrinologists) with a response rate of 81.3%., Main Outcome Measure: The experts' GH treatment recommendations., Results: The physicians reported that approximately 58% of their current patients undergoing GH therapy have classical GH deficiency, while 42% have other conditions. The proportion of physicians who recommended GH treatment of short non-GHD children ranged from 1% to 74% over all case scenarios presented. The likelihood of GH being recommended depended on the physiological growth characteristics of the child (ie, the child's height, growth rate, and predicted adult height), contingency factors (ie, strong family wishes or a reduction in GH cost), and physician beliefs (ie, the impact of short stature on well-being, the effectiveness of GH therapy). Each of these factors exerted highly significant, independent, and additive effects on decisions to recommend GH., Conclusion: Our results indicate that many pediatric endocrinologists consider GH treatment appropriate for selected short non-GHD children, going beyond current Food and Drug Administration-approved indications for GH. Decisions to recommend GH for a non-GHD child rest on a combination of medical, social, and perceptual factors; variations in treatment patterns stem from variations in these influences. Future GH use will likely be determined not only by the results of controlled trials, but also by family preferences, producer pricing, and physician perceptions of the value of height and GH therapy.

Since synthetic growth hormone became available in the mid-1980s, there has been debate about its use for non-growth-hormone-deficient short children. Justification for this use of growth hormone often is based on a presumed association of short stature with significant psychosocial maladjustment. However, systematic evaluation of psychosocial functioning in short children has been limited, and our understanding of this area is scant. In this study, we have used a combination of interview and self-report measures to examine self-esteem, personality characteristics, affective functioning, coping style, and stature-related stresses in 41 children (5 to 16 years) referred to a pediatric endocrinology service because of short stature. Parent-report and child measures of self-esteem and psychological functioning indicated no evidence of maladjustment in comparison with norms. Furthermore, within the subject sample, the degree of short stature was not related to poor psychological functioning. We found limited evidence linking increased age with increased distress, suggesting that short stature may pose greater difficulties for children as they enter adolescence. Taken as a whole, however, the results do not support the contention that short stature is generally associated with psychosocial maladjustment in children referred for evaluation of their short stature.

We designed a prospective study of height potential in girls with idiopathic precocious puberty, comparing the presenting features of girls with and without evidence of reduced adult height potential. The 14 girls with impaired adult height prognoses (group 1) were reexamined after treatment with a gonadotropin releasing hormone agonist, nafarelin. The seven girls with the prognosis of unimpaired height (group 2) were followed without therapy. We found that the group could be distinguished at initial examination by the greater bone age/height age ratio of group 1 (mean +/- SEM: 1.4 +/- 0.06 vs 1.0 +/- 0.05; p less than 0.005) and by the greater difference between predicted height and target height in group 1. The mean predicted height in group 1 was significantly less than the mean target height (150.7 +/- 2.1 vs 165.4 +/- 3.0 cm; p less than 0.005), whereas the mean predicted and target heights in group 2 were similar (165.4 +/- 3.0 vs 164.3 +/- 2.1 cm). Initial estradiol levels were also greater in group 1 than in group 2 (21.6 vs 10.6 pg/ml; p less than 0.05), although this difference was not sustained during follow-up. In group 1, nafarelin therapy suppressed the pituitary-gonadal axis, and although there was a transient reduction in height potential in girls with the youngest bone ages during the first 6 months of therapy, 2 years of treatment slightly improved predicted heights from 150.7 +/- 2.1 to 152.7 +/- 2.0 cm (p less than 0.05). Height predictions also increased without therapy during the 2-year observation period in group 2, from 165.4 +/- 3.0 to 168.7 +/- 4.1 cm (p less than 0.05). Our data indicate that gonadotropin releasing hormone agonist therapy preserves height potential in girls with an initially impaired height prognosis, and that height potential is preserved without therapy in those with a good initial height prognosis.