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Although it has long been recognized that growth hormone (GH) treatment increases
the adult height of those with Turner syndrome, this Canadian study is the
first randomized controlled trial carried through to adulthood. Girls with
Turner syndrome, aged 7–13 years, were randomly assigned to either receive
GH treatment (0.30 mg/kg /wk by subcutaneous injection 6 times per week; n
= 76) or to be a part of an untreated control group (C) that did not receive
GH treatment (n = 78). Sex hormone replacement was used to induce puberty in both cohorts
at age 13 years if onset did not occur spontaneously. Growth hormone treatment
lasted on average 5.7 years. Protocol completion required an annualized height
velocity of <2 cm/yr and a bone age of 14 years or greater. There were 104
patients (61 GH, 43 C) that completed the protocol (50 withdrew). At protocol
completion, mean heights were 147.5 ± 6.1 cm (GH) and 141.0 ± 5.4
cm (C) (P<0.001). Girls who started GH at an earlier age showed a
greater increase in adult height (+0.22 SD, 95% CI 0.10–0.33 SD, or +1.5
cm/yr for each year of earlier GH initiation [P<0.001]), although
this age effect was highly variable between patients. Two follow-up visits further
verified the adult height and assessed safety. For those available at least 1
year after protocol completion (n = 59; 40 GH, 19 C), mean heights were 149.0 ± 6.4
(GH) and 142.2 ± 6.6 cm (C) (P<0.001). The estimated height
gain attributable to GH was +7.2 cm at protocol completion (CI = 6.0–8.4),
and +7.3 cm (CI = 5.4–9.2) at follow-up (at least 1 year after protocol
completion).
This report was accompanied by an editorial by Carel, in which he chronicled
the history of GH treatment for short stature in Turner syndrome. Carel estimated
that height gains across studies ranged from “minimal” to 17 cm
for high-dose GH treatment. He applauded the Canadian researchers for adopting
a powerful research design and carefully following participants. Although he
noted that GH treatment unquestionably increased adult height in women with
Turner syndrome, he posed a number of provocative questions regarding the cost-effectiveness
and safety of GH in this population.
Stephure DK; Canadian Growth Hormone Advisory Committee. Impact of growth hormone supplementation on adult height in Turner syndrome: Results of the Canadian randomized controlled trial. J Clin Endocrinol Metab. 2005;90:3360–3366.
Carel JC. Editorial: Growth hormone in Turner syndrome: Twenty years after, what can we tell our patients? J Clin Endocrinol Metab. 2005;90:3793–3794.
Editor’s Comment: Although some readers may view
the study’s findings as old news, the accompanying editorial highlights
details of its importance. By contrasting these findings with those from a
recently published report of a French population-based cohort of GH-treated
patients,1 several important questions/observations arise, as succinctly summarized
in the Carel editorial. First, insofar as adult height gained (2.7–11.7
cm for those initiating treatment between 7-13 years) varies substantially
across patients, most importantly attributable to age at treatment initiation,
Carel asks whether GH should be used if only a minor effect is anticipated.
Second, Carel claims that adult height gained with GH is not a validated proxy
measure for “quality of life” which he identifies as the primary
rationale for treatment. In his study, 88% of young adult participants favorably
rated their GH treatment. However, when asked to estimate the minimal height
gain they thought would make GH treatment worthwhile, the figure was above
8 cm in 64% of cases. Thus, based on adult heights achieved in the French cohort,
two-thirds of patients treated with GH in the Canadian trial and many other
studies would not consider treatment “worthwhile.” Third, findings
from this study cannot be extrapolated to adult height outcomes that might
be achieved should GH treatment be initiated earlier than 7 years or using
higher doses. Finally, Carel focuses on the safety profile of GH treatment.
He acknowledges that the overall safety record is good, but cites 2 studies
that linked GH therapy with a heightened risk of otitis media. Furthermore,
the presence of hearing difficulties in adulthood was found to be a robust
predictor of a more negative quality of life in Turner syndrome patients. GH
treatment and the associated theoretical risk for cancer was also noted, and
careful monitoring of IGF-I levels and long-term follow-up studies were recommended.
David E. Sandberg, PhD
Reference - (linked to  )
- Carel JC, Ecosse E, Bastie-Sigeac I, et al. J Clin Endocrinol Metab. 2005;90:1992–1997.
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Current GGH - Vol. 24 No. 1
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