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W2035237176 abstract "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 hGH were 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?1.Allen D.B Fost N.C Access to treatment with human growth hormone: proceedings of a conference.Growth Genetics Horm. 1992; 8: 1-76Google Scholar We argued that hGH effectiveness and serious disability rather than the designation of GHD should guide access.2.Allen D.B Fost N.C Growth hormone therapy for short stature: panacea or Pandora's box?.J Pediatr. 1990; 117: 16-21Abstract Full Text PDF PubMed Scopus (85) Google Scholar 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.3.Lantos J Siegler M Cuttler L Ethical issues in growth hormone therapy.JAMA. 1989; 461: 1020-1024Crossref Scopus (77) Google ScholarThe intervening years have in some ways clarified and in some ways complicated this debate.4.Endocrinologist. 2001; 11: 1-86Crossref Scopus (3) Google Scholar 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).5.Endocrinologic and Metabolic Drugs Advisory Committee Notice of Meeting. Food and Drug Administration, HHS.Federal Register. May 6, 2003; 68: 24003-24004Google Scholar 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.6.Rosenfeld R.G Albertsson-Wikland K Cassorla F Frasier S.D Hasegawa Y Hintz R.L et al.Diagnostic controversy: the diagnosis of childhood growth hormone deficiency revisited.J Clin Endocrinol Metab. 1995; 80: 1532-1540Crossref PubMed Google Scholar 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.1. Distinctive ethical challenges of hGH therapyHuman GH therapy has expanded beyond the boundaries of traditional endocrinology, in which missing hormones were replaced and excessive hormone production suppressed. Before 1985, few children with short stature and normal GH secretion received hGH treatment. Today, despite a scarcity of published data showing clear psychologic and social benefit, more than 40,000 children currently receive hGH therapy in the United States. Even before approval for non-GHD conditions, approximately one third were classified by the treating physician as “idiopathic short stature.”7.Guyda H.J Use of growth hormone in children with short stature and normal growth hormone release: a growing problem.Trends Endocrinol Metab. 1994; 5: 334-340Abstract Full Text PDF PubMed Scopus (27) Google ScholarBiosynthetic hGH is expensive, and many ethical considerations regarding its use are inextricably tied to this fact; for example, how should hGH therapy be prioritized in the context of the American health care system that excludes 40 million people from any health insurance? Using traditional dosing guidelines, the annual cost for one child weighing 30 kg is approximately $15,000 to $20,000. Continued treatment of the late pubertal child to maximum adult height, particularly if higher “pubertal” doses are utilized, can exceed $50,000 per year.8.Mauras N Attie K.M Reiter E.O Saenger P Baptista J High dose recombinant human growth hormone treatment of GH-deficient patients in puberty increases near-final height: a randomized, multicenter trial.J Clin Endocrinol Metab. 2000; 85: 3653-3660Crossref PubMed Scopus (184) Google Scholar In the United States, since hGH therapy is now approved for children with height <1st percentile, roughly 40,000 children (1% of an annual cohort of 4 million children born each year) could be considered candidates for treatment each year. Assuming an average of 4 years of treatment at $10,000 to $25,000 per year, expenditures could theoretically reach 1.6 to 4 billion dollars for each cohort of hGH-treated children. Although it is acknowledged that only some fraction of eligible children will receive treatment, it remains clear that those who prescribe or reimburse for hGH treatment must still confront the question whether the benefits of the intervention justify its cost.In contrast to most other hormonal therapies, measuring the benefit of hGH therapy is extraordinarily complex. Enthusiasm for hGH therapy is traditionally rooted in the assumption that short stature is inevitably psychologically disabling and that taller adult stature as the result of hGH therapy will lead to better psychosocial function for these individuals. Both assumptions are currently being challenged. Clearly, short stature at its extreme can be physically disabling, and population differences do exist between short and tall groups with regard to income and access to leadership positions.9.Schumacher A On the significance of stature in human society.J Hum Evol. 1982; 11: 697-701Crossref Scopus (29) Google Scholar, 10.Dannenmaier H Thumin F.J Authority status as a factor in perceptual distortion of size.J Soc Psychol. 1964; 63: 361Crossref PubMed Scopus (54) Google Scholar However, most children currently treated with hGH are not truly physically disabled, and recent analyses have generally failed to demonstrate a relation between adult height of hGH-treated individuals and quality of life.11.Sandberg D.E Quality of life benefits of growth hormone-increased final height: what do we know?.Endocrinologist. 2001; 11: 8S-14SGoogle Scholar Furthermore, the “benefit” of hGH therapy with regard to height gained is relative to the height of others; since social and economic advantages of height only accrue to the hGH-treated person at the expense of another (now relatively shorter) person, the individual's interest in greater height does not necessarily correlate with the societal interest. To be fair, then, should the proper end point of hGH therapy in children be the maximum attainable height or simply a height that allows a child to be within the “normal opportunity range”?12.Daniels N Just health care. Cambridge University Press, New York, NY1985Crossref Google Scholar Or, is height merely a surrogate measure, and should improved psychosocial adaptation be the appropriate criterion for defining hGH treatment's effectiveness? Whatever the possible end point might be, to what extent should insurance or public funds be used to support height-promoting treatment?2. Initiation of GH therapy: justified by diagnosis, disability, or expected outcome?Recent FDA approval of GH therapy for ISS hinged on the argument put forth in our prior study2.Allen D.B Fost N.C Growth hormone therapy for short stature: panacea or Pandora's box?.J Pediatr. 1990; 117: 16-21Abstract Full Text PDF PubMed Scopus (85) Google Scholar that the purpose of GH therapy in most situations is to correct the presumed disability of shortness, regardless of underlying cause. This concept can be invoked to guide not only the initiation but also the restriction of GH therapy. Consider a child with Turner syndrome born to tall parents, with a predicted adult height at or above the 5th percentile (∼5 feet, 0 inches) for adult women. This child would be disabled by short stature equally with other children destined for an adult height at the 5th percentile. Although GH treatment can effectively and safely increase adult height in Turner syndrome13.Rosenfeld R.G Attie K.M Frane J Brasel J.A Burstein S Cara J.F et al.Growth hormone therapy of Turner's syndrome: beneficial effect on adult height.J Pediatr. 1998; 132: 319-324Abstract Full Text Full Text PDF PubMed Scopus (247) Google Scholar and treatment is now considered standard practice, application of the “disability” rather than “diagnosis” criterion suggests that all girls with Turner syndrome should not be entitled to treatment. To their credit, GH manufacturers seeking approval for the ISS indication defined a height threshold of −2.25 SD (∼<1st percentile) as a criterion for consideration for treatment. Although this threshold applied during childhood may not necessarily translate to equally short projected adult short stature, it does represent an effort to define a degree of short stature likely to be associated with disability. Serious evaluation of whether a child is likely to be truly disabled by stature focuses therapy on the most deserving patients and resists treatment of diagnostically “qualified” but nondisabled children. A strictly diagnosis-related approach, in contrast, promotes initiation and prolonged treatment of some nondisabled children who happen to meet a laboratory threshold (eg, stimulated GH <10 ng/mL) or have a well-described disorder with a known cause, such as Turner syndrome. This analysis is consistent with the general axiom that the patient should be the focus of treatment, not a laboratory test.A second important criterion to justify initiation of treatment and to provide adequate informed consent is the reasonable expectation for a clinically significant benefit. A recent meta-analysis suggested that hGH therapy in otherwise normal short children adds between 0.5 to 1 cm to adult height per year of treatment, with an estimated cost of $35,000 per inch.14.Finkelstein B.S Imperiale T.F Speroff T Marrero U Radcliffe D.J Cuttler L Effect of growth hormone therapy on height in children with idiopathic short stature: a meta-analysis.Arch Pediatr Adolesc Med. 2002; 156: 230-240Crossref PubMed Scopus (27) Google Scholar More recent data presented to the FDA indicated that the addition of 2 to 3 inches was possible for hGH-treated children with ISS.5.Endocrinologic and Metabolic Drugs Advisory Committee Notice of Meeting. Food and Drug Administration, HHS.Federal Register. May 6, 2003; 68: 24003-24004Google Scholar However, one could argue that height can only be considered a surrogate measure and that the relevant clinical outcome should be amelioration of physical or psychosocial disability. In contrast to prior assumptions, recent studies have failed to show a relation between adult height and quality of life.15.Sandberg D.E MacGillivray M.H Growth hormone therapy in childhood-onset growth hormone deficiency: adult anthropometric and psychological outcomes.Endocrine. 2000; 12: 173-182Crossref PubMed Scopus (19) Google Scholar Anecdotal experience suggests a beneficial effect of hGH therapy on quality of life in patients with Turner syndrome,16.Rosenfeld G.R Height enhancement in Turner syndrome: is it clinically significant.Endocrinologist. 2001; 11: 15S-17SGoogle Scholar but studies assessing impact on psychosocial function are lacking. The outcome envisioned by patients with Turner syndrome or ISS—achieving a height well within the normal range—does not occur for many children. Although height within the normal range appears achievable for most patients with Turner syndrome in some studies,17.van Pareren Y.K de Muinck Keizer-Schrama S.M Stijnen T Sas T.C Jansen M Otten B.J et al.Final height in girls with turner syndrome after long-term growth hormone treatment in three dosages and low dose estrogens.J Clin Endocrinol Metab. 2003; 88: 1119-1125Crossref PubMed Scopus (188) Google Scholar the mean adult height achieved by patients in 20 trials of hGH treatment of girls with Turner syndrome was only 150.0 cm (∼4 feet, 11 inches).18.Guyda H.J Height enhancement in Turner syndrome (following GH treatment) is often not clinically significant.Endocrinologist. 2001; 11: 18S-24SGoogle Scholar This individual, or a male patient with ISS who reached 5 feet, 3 inches, rather than 5 feet, 1 inch, would still be short, and it remains uncertain whether the increment would have a measurable effect on quality of life.19.Canadian Growth Hormone Advisory Committee GH treatment to final height in Turner syndrome: a randomized controlled trial.Horm Res. 1998; 50: 25SCrossref PubMed Google Scholar Unfortunately, conclusive data regarding this issue from placebo-controlled trials will be extremely difficult, if not impossible, to obtain in the current environment of nearly universal treatment of girls with Turner syndrome. It is critical that this opportunity to assess the value of hGH therapy not be missed for the much larger ISS population.3. End points of hGH therapy: maximum height or normal height?Determining a responsible end point for growth-promoting hGH therapy is also problematic and challenges us to distinguish between what our patients want from what they truly need. Here, too, focusing on disability rather than diagnosis may provide a more coherent framework. Regardless of diagnosis, continuing treatment until the child reaches maximum height is problematic for two reasons: first, because it assumes the child needs such treatment—a medical question—and, second, because it assumes he or she is entitled to it—an ethical question.With regard to the medical problem, treating children diagnosed with IGHD until growth in stature is completed presumes that they need hGH to grow throughout that period. In fact, many children with IGHD treated with hGH (30% to 70%) do not have permanent or complete GHD, nor would they be eligible for continuation of hGH treatment in adulthood if retesting criteria of 5 ng/mL were applied.20.Tauber M Moulin P Pienkowski C Jouret B Rochiccioli P Growth hormone retesting and auxological data in 131 GH-deficient patients after completion of treatment.J Clin Endocrinol Metab. 1997; 82: 352-356Crossref PubMed Scopus (163) Google Scholar Consequently, in children previously diagnosed with IGHD who do not have identifiable central nervous system abnormalities or other pituitary hormone deficiencies, it appears reasonable to periodically reassess the diagnosis of IGHD and to consider interruption of therapy and observation (at the latest) once a height within the normal range has been attained. Cessation of treatment well in advance of maximal height attainment could save years of unnecessary injections and expensive treatment in many children with transient IGHD.Second, it is difficult to defend the claim that every child is entitled to medical care that helps him or her achieve either a height appropriate for/acceptable to family or maximal possible height. Such a proposal would be rejected if it were made on behalf of children without GHD who were already above the 50th percentile but claimed they could achieve even greater height with access to hGH. The reason for rejecting this request is because such a child has no serious disability. Although it might be particularly disappointing for tall parents to have a short child, parental expectations or desires cannot be the basis for entitlement to GH therapy. For the adolescent with GHD who has achieved a height in the normal adult range, the mere fact that he or she could be even taller with continued higher-dose treatment8.Mauras N Attie K.M Reiter E.O Saenger P Baptista J High dose recombinant human growth hormone treatment of GH-deficient patients in puberty increases near-final height: a randomized, multicenter trial.J Clin Endocrinol Metab. 2000; 85: 3653-3660Crossref PubMed Scopus (184) Google Scholar does not justify entitlement to this highly expensive phase of growth-promoting therapy.Children with Turner syndrome, intrauterine growth retardation, or ISS also have some other disease or disorder that precludes a height within the normal range. Today, the understanding of the cause of these growth disorders is less well defined. Nevertheless, both these and children with GHD rightfully claim they are shorter than they could be with treatment. All can claim they have the potential to be taller. However, there does not appear to be a strong claim that either is entitled to growth-promoting treatment beyond what Daniels12.Daniels N Just health care. Cambridge University Press, New York, NY1985Crossref Google Scholar has called the “normal opportunity range.” This concept appeals to our notion that the goal of justice in access to health care has to do with the opportunity to achieve the generally accepted benefits of life in our society. There is no coherent claim that anyone is entitled to communal resources to maximize his/her opportunities, whether in food, shelter, education, health care, or income.A cost-benefit analysis of height gained as a result of hGH treatment suggests that escalating cost is matched with diminishing return.21.Allen D.B Terminating growth-promoting GH therapy: in favor of the “normal opportunity range.” Endocrinologist. 2001; 11: 56S-59SGoogle Scholar Cost per inch rises dramatically as the child grows and receives a higher weight-adjusted dose, estimated at $5000 per inch at ages 5 to 10 years, $15,000 per inch during adolescence, and $20,000 to $30,000 per inch during the last few years of treatment aimed at achieving the genetic potential for growth of the now-heavier adolescent.22.Allen D.B Issues in the transition from childhood to adult growth hormone therapy.Pediatrics. 1999; 104: 1004-1009PubMed Google Scholar Indeed, it appears most efficient to identify and treat early those children who meet criteria for treatment and are expected to be GH-responsive. This needs to be balanced with stopping treatment when there is evidence that the child no longer requires hGH to achieve an adult height in the normal range. To date, no data support improvement in psychosocial outcomes of hGH-treated individuals by the addition of inches of height within the normal adult distribution.23.Rekers-Mombarg L.T Busschbach J.J Massa G.G Dicke J Wit J.M Quality of life of young adults with idiopathic short stature: effect of growth hormone treatment: Dutch Growth Hormone Working Group.Acta Paediatrica. 1998; 87: 865-870Crossref PubMed Google ScholarTo what extent should private insurance or government funds be expected to support the treatment of short stature? Once height no longer considered a handicap (eg, within the statistical normal range) is achieved, one could argue that families could seek continued therapy if they were willing to commit their own resources but that they would not be entitled to communal resources, whether from a private insurance pool or public funds. Our society generally tolerates individual discretion in spending earned income for health matters, particularly if these decisions do not cause severe harm to those who could not afford treatment. Given the apparently modest gains produced by hGH treatment in most non-GHD children, it is unlikely that there would be severe overall harm. The inequality likely to be produced by such private purchases may indeed be trivial as compared with other consequences of inequality of wealth.Perhaps the most useful approach to determining an appropriate end point is to ask at what point a therapeutic successful outcome of hGH treatment has been achieved. Psychologic studies performed in the general population, contrary to the conclusions of prior studies based on referred patients, reveal that short stature, although it may confer disadvantage with regard to income and social status, does not equate a priori with definable physical or psychologic disability.24.Young-Hyman D Effects of short stature on social competence.in: Stabler B Underwood L Slow grows the child: psychosocial aspects of growth delay. Lawrence Erlbaum Associates, Mahwah (NJ)1986: 178-189Google Scholar, 25.Downie A Mulligan J McCaughey E Stratford R.J Betts P.R Voss L.D Psychological response to growth hormone treatment in short normal children.Arch Dis Child. 1996; 75: 32-35Crossref PubMed Scopus (66) Google Scholar Consequently, arbitrary notions about what constitutes nondisabling stature are best set aside in deference to a population's statistically defined norms. Growth-promoting treatment beyond that point makes recipients taller than other normal-stature adults. From a practical standpoint, discontinuation of hGH for children with isolated GHD after a height greater than the adult 5th percentile is achieved will rarely result in a maximum height at that point. More important, treatment stopped when the height is within the normal adult range represents not only a successful therapeutic outcome but also reasonable allocation of resources and preservation of a proper goal for medicine.From an ethical standpoint, the distinction between treatment and enhancement might be useful in addressing other questions of entitlement in medical practice (eg, repair of deforming congenital facial anomalies versus facelifts).26.Daniels N Growth hormone therapy for short stature: can we support the treatment/enhancement distinction?.Growth Genetics Horm. 1991; 8: 46-49Google Scholar, 27.Fost N.C Access to GH therapy: is the treatment/enhancement distinction useful?.Endocrinologist. 2001; 11: 72S-77SGoogle Scholar But there are hazards in trying to resolve all questions of access by relying on traditional distinctions between health and disease and between treatment and enhancement. Some conditions are clearly diseases, such as the persistent vegetative state, but might not warrant expensive prolonged treatment. Similarly, some conditions are clearly not diseases, such as pregnancy, and yet attract wide support for treatment to be included in a basic benefits package. Consequently, some treatments do not warrant funding and some enhancements do. The latter could include bringing “normal” short children into the normal height range.28.Buchanan A Growth hormone: a paradigm of expansive biotechnologies.Endocrinologist. 2001; 11: 78S-82SGoogle Scholar4. GH gatekeepers: weighing individual and societal interestsBuchanan28.Buchanan A Growth hormone: a paradigm of expansive biotechnologies.Endocrinologist. 2001; 11: 78S-82SGoogle Scholar observed that hGH is a paradigm of “expansive biotechnologies,” referring to technologies that begin as medical treatments for severely disabling conditions but then are found to offer benefits that do not so clearly belong in the health care system. Few would dispute that pituitary dwarfism is a medical problem warranting medical treatment, but many of the newer applications of hGH, such as producing marginal increments in height or improving strength (eg, for Prader-Willi syndrome),29.Carrel A.L Allen D.B Prader-Willi syndrome: how does growth hormone affect body composition and physical function?.J Pediatr Endocrinol. 2001; 14: 1S-10SCrossref Google Scholar are not so clearly defined as medical problems. As such, hGH can be compared with other technologies including artificial insemination and Prozac, which began as treatments for serious medical problems but expanded to much larger markets that involved problems that were less clearly medical. These expanding uses for very expensive technologies “erode our society's already shaky commitment to the right of a decent minimum level of health care for all.”28.Buchanan A Growth hormone: a paradigm of expansive biotechnologies.Endocrinologist. 2001; 11: 78S-82SGoogle Scholar“Affordable” hGH would not solve the problem of defining responsible prescription of hGH treatment. Pediatric endocrinologists readily admit that the continued high cost of hGH confers a certain protection from even more complex dilemmas of equitably restricting hGH when families of children desirous of ongoing hGH therapy do not require insurance reimbursement to pay for it. Thoughtful pediatricians have also questioned the claim that treatment with hGH is a net benefit, particularly for children without GHD. In view of unclear psychosocial benefit, more consideration should be given to the potential psychologic harm of an implied message to children that their parents are not accepting of them.30.Diekema D.S Is taller really better? Growth hormone therapy in short children.Perspect Biol Med. 1990; 34: 109-123PubMed Google Scholar The physician should also be concerned about disappointment (ie, the risk of “unmet expectations”) when the child commonly fails to achieve the increase in height that was originally hoped.To determine the value and therefore the justification for hGH therapy in various conditions, a clearer formulation of the ultimate end points sought is needed. Height cannot be the sole appropriate end point because, in the words of Brock, “it is only instrumental to improvements in patients' quality of life.” He urges that future studies focus on quality-of-life gains because coverage by insurance would be difficult to justify without clearly establishing these benefits.31.Brock D Growth hormone treatment: summing up the issues.Endocrinologist. 2001; 11: 83S-89SGoogle Scholar5. ConclusionsMore than a decade ago, we devised the cases of Johnny and Billy to frame the ethical issue of entitlement to hGH:“Johnny is a short 11 year-old boy with low GH levels and a predicted adult height without GH treatment of 5 feet, 3 inches. Billy is an equally short boy with normal GH levels who also has a predicted adult height of 5 feet, 3 inches.”2.Allen D.B Fost N.C Growth hormone therapy for short stature: panacea or Pandora's box?.J Pediatr. 1990; 117: 16-21Abstract Full Text PDF PubMed Scopus (85) Google ScholarSince then, some hotly contested issues have been clarified. It is no longer disputed that the underlying cause is not morally relevant in deciding who is entitled to treatment. Similarly, the “treatment/enhancement” distinction cannot do the moral work of telling us who is entitled to treatment. Billy and Johnny are equally entitled to hGH treatment if it is safe and effective, and now “Tina” with Turner syndrome is considered entitled to treatment. In other words, children with comparable growth impairment should be considered morally equivalent when it comes to hGH treatment. The central question that remains, for all of these children, is what degree of short stature is sufficiently disabling to warrant treatment, and if so, up to what height? In short, for whom do we start hGH treatment and when do we stop? To further complicate the matter, we are now confronted with “Peter” with Prader-Willi syndrome, who would like to be stronger and leaner than he is, and an uncounted number of others with Down syndrome,32.Anneren G Tuvemo T Gustafsson J Growth hormone therapy in young children with Down syndrome and a clinical comparison of Down and Prader-Willi syndromes.Growth Horm IGF Res. 2000; 10: S87-S91Abstract Full Text PDF PubMed Scopus (23) Google Scholar spina bifida,33.Trollmann R Strehl E Wenzel D Dorr H.G Does growth hormone (GH) enhance growth in GH-deficient children with myelomeningocele?.J Clin Endocrinol Metab. 2000; 85: 2740-2743Crossref PubMed Scopus (25) Google Scholar and innumerable other conditions who might benefit from treatment with hGH.In conclusion, the analysis above leads us to propose the following guidelines for hGH treatment of short stature:1.Access to hGH should be guided by identification of disability attributed to shortness rather than by a diagnosis associated with shortness.2.Ultimate benefits of hGH-induced increases in height remain an open question, but there is some degree of short stature that constitutes a definable disability and warrants consideration of intervention. 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