Growth hormone therapy in childhood-onset growth hormone deficiency: adult anthropometric and psychological outcomes.

Abstract

The current adult heights of hypopituitary children treated with recombinant human growth hormone (rGH) now range between -1.5 and -0.7 height standard deviations (Ht SDS) of control populations. These height outcomes are markedly better than the ones observed following treatment with pituitary-derived human growth hormone (pGH) (between -4.7 and -2.0 Ht SDS). Although treatment with rGH has not yielded adult heights that are equal to genetic target heights, the discrepancy is much less now than in previous decades. Higher rGH dose, longer duration of treatment, early age at diagnosis, correction of height deficit prior to onset of puberty, and daily rGH injections have had beneficial effects on final adult heights. The current dosing regimens (0.3-0.18 mg/kg/wk) have not had an adverse effect on bone maturation and have not stimulated an earlier onset of puberty. Although height gains in puberty are less than controls, a majority of treated subjects reach heights within the normal range for adults. Higher doses of rGH during puberty have been studied in limited numbers of adolescents with positive effects; however, standard dosing will likely continue to be used because of financial considerations and safety concerns. Further improvements in adult heights are likely to be reported when the youngest children who began rGH in 1985 complete their growth. Several studies have investigated the quality of life (QOL) of GH-deficient (GHD) patients who, as children, had been treated with GH predominantly during the pGH era. Domains of functioning assessed include educational attainment, employment, and marital status. Although some studies have reported a generally positive adaptation, others have shown this group to exhibit marked deficits. Limited adult height outcomes in the pGH era of GH therapy has sometimes been used to account for poor outcomes. Variable behavioral findings are likely related to sample heterogeneity and disparate research methodologies and designs, most particularly the choice of control or comparison groups. In addition to summarizing this older literature, we report on a recently completed investigation in which the QOL adjustment of GHD patients is compared to that of same-sex siblings. Comparisons between GHD cases 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. IGHD (isolated growth hormone deficiency) patients were functioning better than those with MPHD (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.