Growth Hormone Therapy for Short Stature: Is the Benefit Worth the Burden?

In 1985, approval of recombinant human growth hormone (rhGH) made available a virtually unlimited resource to replace human pituitary–derived GH, which had been withdrawn for safety concerns. During the ensuing 2 decades, clinical trials spearheaded by pediatric endocrinologists and supported primarily by manufacturers of rhGH strived to show that rhGH treatment could improve growth rates and eventual height in children without growth hormone deficiency (GHD) who are short as a result of (sequentially) Turner syndrome (TS), chronic renal insufficiency (CRI), small for gestational age (SGA), Prader-Willi syndrome (PWS), or idiopathic short stature (ISS). Approval of these new indications validated the notion, first proposed in 1990,1 that if rhGH treatment is effective at increasing height in non-GHD children, then the etiology of short stature is not morally relevant in deciding who is entitled to treatment. These children all share a central and seemingly valid concern: “I am short and I would like to be taller.” The difficulty is that the phrase “like to be taller” in this context ranges in meaning from “physically need to be taller” to “would feel better if I were taller” or “would make my parents feel better if I were taller.” The key questions are: Which conditions, if any, lead to a degree of short stature that is sufficiently disabling to warrant medical treatment? If any are sufficiently disabling, what final height should be sought? If height is largely a surrogate outcome for improved quality of life, analysis of therapeutic value of rhGH therapy for short stature requires not only examination of effects on adult height but also of the rationale for intervention itself (ie, presumed disability resulting from short stature), whether improved height actually leads to better psychosocial outcomes, and how benefits compare to risks and costs. As discussed below, recent studies provide information … Address correspondence to David B. Allen, MD, Department of Pediatrics, University of Wisconsin Children's Hospital, H4/448 CSC–Pediatrics, 600 Highland Ave, Madison, WI 53792-4108. E-mail: dballen{at}wisc.edu