What is the efficacy of medical treatment for short stature?

Updated: Jan 06, 2021
  • Author: Sunil Kumar Sinha, MD; Chief Editor: Robert P Hoffman, MD  more...
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Medical care depends on the etiology of the short stature.

Recombinant human growth hormone (rhGH) administration has not been proven to remarkably improve final adult height in children with normal variant short stature. [2, 3] Published clinical studies that have focused on this particular issue have been inconclusive. These reports were flawed because of the following:

  • Selection bias due to high drop-out rates from treatment regimens (presumably due, in part, to the parents' or health care provider's dissatisfaction with results of therapy in these individuals)

  • Lack of key design elements for a proper clinical trial (eg, placebo controls, double blinding, randomization)

  • Inadequate follow-up study to final adult height

A double-blinded, randomized study from the National Institutes of Health suggests GH has a small effect on adult height in children with normal short stature if they are treated with GH injections for many years. [11]

Other randomized studies have shown variable results, with some demonstrating benefit [12]  and others not. [13, 14]  A study by Schena et al indicated that in children with short stature who are not GH deficient (ie, those with idiopathic short stature), long-term treatment with rhGH yields results similar to those in GH-deficient children who undergo this therapy, although this study did not have an untreated control group and pretreatment growth velocity data for the patients was missing. [15]  Thus, the risk-benefit ratio for treatment of children with idiopathic short stature is not well defined.

In a randomized, placebo-controlled trial, Shemesh-Iron et al found that among prepubertal boys with idiopathic short stature, those who underwent GH therapy demonstrated improved psychosocial functioning in contrast to those who received a placebo. Results included significantly improved scores on the Rosenberg Self-Esteem Scale (RSES) and the Single-Category Implicit Association Test for height (SC-IAT-H), although scores on the Pediatric Quality-of-Life Inventory (PedsQL) and Child Behavior Checklist (CBCL) did not change. [16]

However, a prospective, observational study by González Briceño et al found that PedsQL scores, as well as scores on the Quality of Life in Short Stature Youth (QoLISSY) questionnaire, improved in children with short stature who were treated with GH, indicating significant increases in emotional and social quality of life. Although the investigators could not rule out a placebo effect, since this was not a placebo-controlled trial, they reported that improvement in QoLISSY questionnaire results moderately correlated with increases in height standard deviation scores (SDS). [17]

Along with questions regarding the benefits of GH therapy, there is also controversy regarding GH dosing. Fixed dosing based on weight has long been used. However, a 2-year, open-label, randomized trial that measured the response to somatotropin (rDNA origin) therapy based on serum insulinlike growth factor-I (IGF-I) levels in children with GH deficiency and in children with idiopathic short stature suggested that IGF-based dosing of GH may safely provide superior growth outcome in both groups. [18]

Recombinant human GH has been used for over 4 decades, with a good track record of safety. A preliminary report from the French part of the European Union Safety and Appropriateness of GH treatments in Europe (EU SAGhE) study showed increased overall mortality in adults treated with rhGH during childhood, raising concerns about the long-term safety of this therapy. [19] Data from Belgium, The Netherlands, and Sweden, however, did not show a similar distribution of causes of death. [20] After reviewing information from the EU SAGhE study and other sources, the US Food and Drug Administration (FDA) recommended continued rhGH prescription and use according to the labeled recommendations. [21]

A study by Miller et al suggested that in males with GHD or idiopathic short stature, combined treatment with GH and aromatase inhibitor (with the latter known to delay epiphyseal fusion) allows ongoing growth over a 2-year period. In the patients with idiopathic short stature, the mean height SDS was -2.15 at baseline, -1.04 before initiation of aromatase inhibitor therapy, and -0.65 after 2 years of concomitant aromatase inhibitor treatment. [22]

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