Growth Hormone

Therapy in Turner's Syndrome

Impact of Injection Frequency and Initial



Ciska Rongen-Westerlaken, MD; An van Es, MD; Jan-Maarten Wit, MD; Barto J. Otten, MD; Sabine M. P. F. De Muinck Keizer-Schrama, MD; Nick M. Drayer, MD; Wilma Oostdijk, MD; Henriette A. Delemarre-vd Waal, MD; Margreet H. Gons, MD; Johan J. J. Waelkens, MD; J. Leo Van den Brande, MD

Study Objective.\p=m-\To determine the influence of the in-

jection frequency and the initial bone age on the efficacy of

tions vs 8.6 cm (3.4 cm) with three injections; the increment in height standard deviation score was 0.9 cm (0.5 cm) vs




treatment with

biosynthetic growth

hormone in Turner's

Design. \p=m-\Randomized study. Setting. \p=m-\Referral-based pediatric endocrinology departments of seven university medical centers. Patients. \p=m-\Fifty-two patients with Turner's syndrome confirmed with chromosomal analysis. Treatment.\p=m-\Somatropin recombinant DNA (24 IU/m2 of body surface area) subcutaneously administered in three or six injections per week for 2 years. Patients who were older than 12 years at the beginning of the study received low doses of estrogen. Results.\p=m-\The following statistically significant findings supported the use of six injections per week compared with three injections per week: the mean (\m=+-\SD)increment in height during 2 years was 11.3 cm (3.8 cm) with six injec-

number of short-term studies have in¬ In dicatedyears that administration of human growth hor¬ with increase the of recent


(GH) can


growth velocity


Turner's syndrome.1"3 Growth hormone was adminis¬ tered in three injections per week in two studies1-2 but in seven injections per week in a previous study by our group.3 The superior results in terms of increment in growth velocity encountered in the latter study suggested a positive effect of higher injection frequency, in accor¬ dance with the findings in GH-deficient children." How¬ ever, there were age or dosage differences between the studies and we believed that a controlled study was needed to clarify this issue.


for publication January 27, 1991. Departments of Pediatrics, University of Utrecht (Drs Rongen-Westerlaken, van Es, Wit, and van den Brande); University of Nijmegen (Dr Otten); University of Rotterdam (Dr De Muinck Keizer-Schrama); University of Groningen (Dr Drayer); University of Leiden (Dr Oostdijk); Amsterdam Free University (Dr Delemarre-vd Waal); University of Amsterdam (Dr Gons); and Catharina Hospital, Eindhoven (Dr Waelkens), the Netherlands. Reprint requests to the Department of Endocrinology, Wilhelmina Childrens Hospital, Postbox 18009, 3501 CA Utrecht, the Netherlands (Dr Rongen-Westerlaken). From the

0.6 cm (0.3 cm); the growth velocity was 6.6 cm/y (2.0 cm/y) 5.2 cm/y (1.7 cm/y) in year 1 and 4.7 cm/y (2.0 cm/y) vs 3.4 cm/y (1.7 cm/y) in year 2; and the increment in height standard deviation score for bone age was 0.8 cm (0.5 cm) vs 0.4 cm (0.6 cm). For patients whose initial bone age was more than 13 years, growth velocity increased by 1 to 2 cm in year 1; in year 2 no increment was observed. We did not

observe adverse effects. Conclusions. \p=m-\Biosynthetic growth hormone in a higher\x=req-\ frequency regimen in Turner's syndrome is more efficient in terms of increment in height, growth velocity, and height standard deviation score for bone age than treatment in a lower-frequency regimen. In patients with an initial bone age of more than 13 years, the response was poor. Longer follow-up is necessary to assess the effect on final height.

(AJDC. 1992;146:817-820)

In addition to the uncertainty about the effect of the in¬ jection frequency, there are few data available about the age or bone age limits below which GH therapy can result in a substantial height gain. We report herein the results

of a 2-year study on the impact of injection frequency, age, and bone age on the efficacy of GH therapy. PATIENTS AND METHODS

Fifty-four girls with Turner's syndrome entered the study. The study was approved by the medical ethical committees of all participating hospitals. The inclusion criteria were as follows:

age older than 6 years, bone age (Tanner-Whitehouse-20 bones)7 below 14 years, and diagnosis of Turner's syndrome confirmed with lymphocyte chromosomal analysis (Y chromosome mate¬ rial was not accepted). Ages ranged from 6.7 to 18.9 years and bone ages ranged from 3.8 to 13.6 years. The children were divided into groups with a chronological age of younger than 12 years and a chronological age of 12 years or older. All children received biosynthetic GH at 24 IU/m2 of body surface area per week (Humatrope, somatropin recombi¬ nant DNA, Lilly, Indianapolis, Ind; 1 IU 2.7 mg), correspond¬ ing to approximately 0.8 IU/kg per week. Patients were ran¬ domly assigned to a regimen of either 8 IU/m2 of body surface area three times a week (group 1) or 4 IU/m2 of body surface area six times a week (group 2). Patients older than age 12 years at the

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Table 1.—Selected

Auxological Age

Parameters at the Start of Treatment*

12 y -1 6


per Week 16

Age, y

13.0 (0.4)§ 12.2 (1.2)§ 8.3(2.3) 9.2(1.4) Bone age TW-RUS, y 8.6(2.5) 13.2(0.6) 9.5(1.6) 12.4(1.1) 119.2 (7.9) 122.8 (9.6) 142.9 (5.4) 138.0 (7.6) Height, cm 0.04(0.7) 0.4(0.9) 0.7(1.1) 0.6(0.7) Height SDSt SDS* -3.4 -3.0 -3.8 -3.8 (0.6) (0.6) (0.9) (0.5) Height 4.0 4.2 3.0 3.4 (1.0) (1.4) (1.0) (1.1) Height velocity, cm/y SDS for bone age 0.1(1.0) 0.9(0.9) 0.0(1.2) 0.6(0.8) Height 145.5 (5.9) 145.8 (3.8) 149.7 (5.4) 147.0 (5.0) Height prediction, cm *Data are mean ( ± SD) unless otherwise indicated. In both age groups, patients receiving three injections per week were compared with patients receiving six injections per week for statistical significance. TW-RUS indicates Tanner-Whitehouse radius ulna short bones; and

SDS, standard deviation



references for patients with Turner's *Dutch girls without a growth disorder.

syndrome, according to

Ranke et

al,8 were used


calculate the




Growth hormone therapy in Turner's syndrome. Impact of injection frequency and initial bone age.

To determine the influence of the injection frequency and the initial bone age on the efficacy of treatment with biosynthetic growth hormone in Turner...
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