hGH for short stature: ethical issues raised by expanded access☆

When the only source of therapeutic human growth hormone (hGH) was pituitary-derived GH, rationing of this precious resource was a necessity. Recombinant DNA technology made hGH abundant, but this abundance also brought uncertainty, controversy, and discomfort to practitioners trying to practice ethically responsible medicine. Early debates focused on two central questions: (1) If hGHwere proven effective at increasing the height of children without GH deficiency (GHD), would the diagnosis of GHD be morally relevant in determining entitlement to hGH treatment? (2) Regardless of underlying cause, should the treatment of short stature be considered a medical problem justifying medical treatment, and, if so, to what degree? We argued that hGH effectiveness and serious disability rather than the designation of GHD should guide access. Others countered that patients with GHD had a disease deserving treatment, whereas children short from other causes did not have a disease (at least not that of GHD) and that to treat them would constitute enhancement and not therapy. The intervening years have in some ways clarified and in some ways complicated this debate. hGH has been approved by the Food and Drug Administration (FDA) for treatment of non–GH-deficient children with Turner syndrome, chronic renal insufficiency, short stature caused by intrauterine growth retardation, and, most recently, children with severe familial or idiopathic short stature (ISS). Thus, there is now consensus that the cause of short stature is not morally relevant in deciding who is entitled to treatment. The utility of GHD as a necessary or sufficient criterion for eligibility for treatment is a priori problematic, since the definition and ascertainment of GHD is still controversial and elusive. Isolated GHD (as conventionally diagnosed) is usually neither complete nor permanent. A continuum of GH secretion spans the clinical presentations of ‘‘partial’’ versus ‘‘severe’’ isolated GHD versus ‘‘complete’’ (ie, multiple pituitary hormone deficiency state) GHD. Children with isolated GHD (IGHD) without identifiable central nervous system abnormalities or metabolic evidence indicative of severe GHD (eg, hypoglycemia or abnormal body composition) comprise the majority of and most controversial hGH-treated patients. In the discussion below, ‘‘GHD’’ refers to these patients, not to severe, permanent GHD associated with hypoglycemia, identifiable central nervous system malformations, or multiple pituitary hormone deficiencies. In addition to proving the irrelevance of underlying cause, this transformation in practice has unmasked the limited relevance of the treatment/enhancement distinction in determining who is entitled to treatment. Defenders of this distinction argued that the non-GHD child did not have a disease and that the use of hGH in such a situation constituted enhancement, implicitly an inappropriate goal of the practice of medicine. Today, it is acknowledged that the non–GH-deficient child’s central concern is identical to that of the child with GHD; namely, ‘‘I am short and I would like to be taller.’’ To the child and the parent, it is irrelevant whether the condition being treated is a well-characterized ‘‘disease’’ caused by GHD or a less well-understood process, as is the case in Turner syndrome and ISS. If ‘‘enhancement’’ refers to a desire for a child to be taller than he would be if left alone, then all children involved in this debate are seeking enhancement. The object of concern is not GH deficiency but short stature, and the only relevant question is whether there is safe, effective, affordable treatment. From the Department of Pediatrics, University of Wisconsin Medical School, Madison, Wisconsin. Dr Allen serves as a grant reviewer for the Genentech Center for Research and receives research grant support from Genentech, Inc, and Eli Lilly, Inc. Submitted for publication Sept 15, 2003; last revision received Jan 15, 2004; accepted Feb 18, 2004. Reprint requests: David B. Allen, MD, Professor of Pediatrics, H4/448 CSC– Pediatrics, 600 Highland Ave, Madison, WI 53792-4108. E-mail: dballen@wisc.edu. J Pediatr 2004;144:648–52. 0022-3476/$ see front matter Copyrighta 2004 Elsevier Inc. All rights reserved.