Final Height of Growth Hormone(GH)-Treated Short Children Registered at the Foundation for Growth Science in Japan: Comparison between the Pituitary Human GH Era and the Recombinant Human GH Era.

The final heights of 2,526 GH-treated short children (1,475 boys and 1,051 girls) who were registered with the Foundation for Growth Science were analyzed. The patients were divided into two groups according to the year of the start of GH treatment: Group P consisted of 1,325 patients (826 boys and 499 girls) who started GH treatment with pituitary derived human GH (phGH) before 1989, when recombinant human GH (rhGH) became available; Group R consisted of 1,201 patients (649 boys and 552 girls) who started GH treatment in or after 1989 and received rhGH. The patients were subdivided into an additional three groups according to gonadal function, and the presence or absence of gonadal suppression treatment (GST): Group A consisted of 1,769 patients (1,089 boys and 680 girls) with isolated growth-hormone deficiency (IGHD) who developed spontaneous puberty and did not receive GST; Group B consisted of 508 patients (253 boys and 255 girls) with IGHD who developed spontaneous puberty and did receive GST; and Group C consisted of 251 patients (133 boys and 118 girls) with multiple pituitary hormone deficiency (MPHD) who did not develop spontaneous puberty and who also received gonadal replacement treatment. Mean final height was significantly taller in Group R than in Group P in both boys (P: 157.9 ± 7.4 cm, R: 160.3 ± 6.1 cm, p<0.0001) and girls (P: 145.5 ± 6.8 cm, R: 147.8 ± 5.4 cm, p<0.0001). In Group A, mean final height was taller in Group R-A than in Group P-A in both boys (P: 157.2 ± 7.5 cm, R: 160.5 ± 5.8 cm, p<0.0001) and girls (P: 145.3 ± 6.9 cm, R: 147.8 ± 5.4 cm, p<0.0001). In Group B. mean final height was significantly taller in Group R-B than in Group P-B in girls (P: 144.4 ± 6.8 cm, R: 147.6 ± 4.8 cm, p<0.0001), but showed no significant difference in boys (P: 157.3 ± 7.1 cm, R: 159.0 ± 7.3 cm). In Group C, mean final height was not significantly different in either boys (P: 162.4 ± 6.0 cm, R: 161.2 ± 7.8 cm) or girls (P: 148.3 ± 5.7 cm, R: 147.2 ± 7.0 cm). Mean final height in Group B (boys: 157.8 cm, girls: 145.8 cm) was not taller than Group A (boys: 158.8 cm, girls: 146.8 cm), but pubertal height gain was significantly greater in Group B (boys: 18.4 cm, girls: 14.0 cm) than in Group A (boys: 13.9 cm, girls: 10.3 cm). Mean final height was the tallest in Group C (boys: 162.1 cm, girls: 147.9 cm). The taller final height in Group R than Group P is mainly attributable to the greater height SDS at the start of GH treatment, since the increase in height SDS during GH treatment was not greater in Group R than in Group P. The improved modalities of GH treatment, such as increased frequency of subcutaneous injection and higher GH dose also contributed to the improved final height in Group R-A and Group R-B, since the height velocity was significantly greater and height at the onset of puberty was taller in Group R than Group P. Since pubertal height gain was greater in Group B than in Group A, it can be concluded that GST was effective. Although the final height was not greater in Group B than the Group A, the final height in Group B would have been much shorter without GST than it was with it. The taller final height in Group C was caused by bone age delay due to hypogonadism and by delaying the induction of puberty. The optimal treatment is therefore whatever permits the patient to catch up with and reach normal height before the onset of puberty, since total pubertal height gain is not greater in GH-treated short children than in untreated short children. Early diagnosis and treatment is therefore important to permit early catch-up with normal height before puberty.