Turner syndrome (TS) is a disorder with distinct clinical features resulting from the complete or partial absence of one of the X chromosomes in females. The incidence is estimated to occur in 1 out of 2,500 live births¹⁾. The manifestations may vary according to the range of chromosomal aberration. However, hypergonadotropic hypogonadism occurs in virtually all affected individuals and short stature is a major confronting issue among patients. The mean adult height in untreated patients is approximately 20 cm shorter than that of the general female population^2,3).

Impaired response to growth hormone (GH) is thought to be the major cause of retarded growth in TS subjects rather than GH deficiency⁴⁾. Although recombinant human growth hormone (hGH) has been prescribed to improve adult height in TS patients for decades^5-7), only a few case-control studies have addressed the effect of hGH administration on the individual and the optimal age for commencement of hGH has not been established yet. Recent studies have suggested that initiating hGH treatment at a younger age is more effective^8-10).

This study is a retrospective analysis of patients with TS who were treated with hGH for more than three years. We investigated factors that were associated with the height response to the treatment.

This study was performed to identify the effect of hGH on subjects with TS and to find clinical factors that may be associated with the outcome of the hGH administration. The height gain was greatest in the first year of treatment and it was negatively associated with the age of commencement. The differences in the subjects'karyotypes did not affect the outcome of hGH administration or the height gain. Although subjects with variant karyotypes showed a slight tendency towards more accretion in height SDS, this was not statistically significant. This finding is compatible with previous reports^13-15).

It has been reported that the age at commencement of hGH therapy and initial height SDS were negatively correlated with height gain, while MPH SDS had positive correlation with the growth outcome^13,14,16). Sas et al.¹⁷⁾ demonstrated that high doses of hGH improved adult height in TS patients. In this study, the age at commencement of hGH treatment and height SDS at the third year showed the negative correlation during the treatment period.

Short stature is the most common clinical presentation in girls with TS. The correction of short stature is reported as beneficial for the patient's quality of life¹⁸⁾ and psychological adjustment may be achieved through the height gain, resulting in improved social competence. Girls with TS show growth failure during early childhood. The height gain in affected girls deteriorates during puberty and they usually do not have the normal pubertal growth spurt. The etiology of growth failure in TS is not well understood. Some studies^19-21) reported that GH secretion decreased in subjects with TS whereas normal GH secretion was observed by other authors^22,23). It is not clear whether the retarded growth is a result of resistance to GH or GH deficiency. It is supposed that haploinsufficiency of the short stature homeobox (SHOX) gene contributesmore to the short stature than a GH-IGF axis disturbance^{24, 25)}.The SHOX gene, which is located on the distal end of the X chromosome at Xp22.3 in the pseudoautosomal region 1, is known to act as a repressor of growth plate fusion. Although short stature and premature ovarian failure are virtually universal findings in patients with TS, recent studies suggest that the distal short arm of the X chromosome are mainly responsible for growth in affected girls, and deletion of proximal region of the X chromosome contributes to the deterioration of ovarian function^26,27).

The additional height improvement in TS patients with hGH administration varies between 1 cm²⁸⁾ to 10 cm^29,30). Chung et al.³¹⁾ reported that 29 Korean patients with TS who were treated with hGH were 4.1 cm taller than who did not. Shin et al.³²⁾ observed 3.4 cm increment of final height in 121 Korean patients with TS. As with heightgain after hGH administration in patients with idiopathic GH deficiency, subjects with TS appear to be most efficacious during the first year of treatment³³⁾. Bakker et al.³⁴⁾ observed that younger subjects in the first year of hGH treatment demonstrated better results in their growth. The height gain in the subjects of this study was also greatest in the first year of treatment and more profound in younger patients. The height of the patients who started the treatment before 12 years of age increased 5.6 to 12.3 cm whereas those who received treatment after 12 years of age only gained 4.5 to 5.8 cm in height during the first year.

Davenport et al.³⁵⁾ demonstrated that hGH administration for patients with TS aged between 9 months and 4 years was followed by attained height SDS within the normal range, whereas the height SDS of nontreated control patients continuously decreased. Linglart et al.³⁶⁾ also reported patients receiving treatment before 4 years of age could achieve height gain without significant adverse effects. Early intervention for height improvement has a number of benefits in girls with TS, such as improvement in their relationships with peers, better self-image, and estrogen replacement at an appropriate age. While an earlier study³⁷⁾ reported that growth of girls with TS is preserved during their preschool age, it is now accepted that growth failure begins even in the first few years of life^38,39).

In this study, the proportion of subjects with monosomy X was much lower than the known prevalence because this study was not a population-based trial. A recent study reported that the incidence of adverse events with hGH administration, such as increased intracranial pressure or slipped capital femoral epiphysis was higher in subjects with TS than in those for other indications⁴⁰⁾. Though no adverse events with the hGH administration were reported during the treatment period, this study is retrospective in design so loss to follow-up can be assumed.

In conclusion, early treatment of hGH in patients with TS seems to be essential for significant height gain and careful monitoring should accompany hGH treatment in patients with TS.