Adult Height in Children With Growth Hormone Deficiency Who Are Treated With Biosynthetic Growth Hormone: The National Cooperative Growth Study Experience

Abstract

Objective. To determine whether the height gain during puberty in children with growth hormone deficiency (GHD) who are treated with biosynthetic growth hormone (GH) is similar to that in otherwise healthy children with delayed bone ages and whether the height standard deviation score (SDS), which began to increase before puberty, continues to increase during puberty. Methods. The inclusion criteria included a diagnosis of idiopathic GHD, prepubertal on enrollment in the National Cooperative Growth Study, and spontaneous onset of puberty, as defined by Tanner stage 2 breast development in girls and a testicular volume of at least 3 mL in boys. Near-adult height was judged to have been attained in the subjects who had reached a chronologic age of at least 18 years (females) or 20 years (males) or had reached at least pubertal stage 4 and a chronologic age of at least 14 years (females) or 16 years (males). These subjects constituted group 1. Group 2 was a subgroup of these subjects who met a more stringent criterion for near-adult height; in addition to meeting the above criteria, they had to have attained a bone age of at least 14 years (females) or 16 years (males). Results. Group 1 consisted of 480 males and 194 females. Group 2 consisted of 153 males and 105 females. In the subjects in group 1, the Tanner pubertal stage 2 was 14.1 ± 1.5 years in males and 12.6 ± 1.6 years in females; the bone age at this stage was 11.9 ± 1.5 years in males and 10.6 ± 1.5 years in females; and the height SDS was −2.1 ± 0.9 in males and −2.4 ± 0.9 in females. The total height gained during puberty was 22.4 ± 7.9 cm in males and 17.4 ± 6.3 cm in females; the percentage of adult height gained during puberty was 13.3% ± 4.6% in males and 11.3% ± 4.0% in females; the near-adult height SDS was −1.3 ± 1.0 in males and −1.6 ± 0.9 in females; and the target adult height SDS was −0.4 ± 0.8 in males and −0.5 ± 0.7 in females. The growth characteristics in the subjects in group 2 were of similar magnitude. In both groups, there was a significant negative correlation between age at the onset of Tanner stage 2 and both the total height gained during puberty and the percentage of adult height gained. Conclusions. The growth characteristics of these subjects were similar to those reported in normal children and in previous reports of the pubertal growth in smaller populations of children with GHD. The height SDS increased in these subjects during puberty, but the target adult height SDS was not attained. This is a strong argument for early diagnosis and treatment in children with GHD to optimize prepubertal growth.

Evolving growth hormone deficiency: proof of concept

“…compared studies between GHD and ISS patients on GH therapy of which one study reported a height gain of 1.3 SDS over an average of 4.6 years in patients with IGHD while another study reported a gain of only 0.5 SD in patients with ISS over an average of 4.4 years ( 24 ). Both the KIGS and NCGS GHD patient cohorts reported mean adult height SDS of -3.1 to 0.2 SDS ( 40 ) and -0.7 ± 1.3 ( 41 ) respectively, lower than our data after 8.1 years and 4.6 years respectively. Furthermore, Loche et al.…”

Endocrine Disorders.

“…Medical treatment of GHD (and all other approved indications for rhGH) entails daily subcutaneous injections. Early initiation of treatment and appropriate dosing can allow youths to achieve full growth potential (August, Julius, & Blethen, 1998;Mauras, Attie, Reiter, Saenger, Baptista, & the Genentech Inc. Cooperative Study Group, 2000).…”

Spotlight on Lonapegsomatropin Once-Weekly Injection and Its Potential in the Treatment of Growth Hormone Deficiency in Pediatric Patients

“…3 It is likely that reduced adherence to daily injections limits treatment outcomes as evidenced by adult height in children who required GH replacement therapy that are below the mean for the population. [4][5][6][7][8][9][10] Maintenance of treatment adherence with daily GH (DGH) injections has also been shown to be problematic for adults with GHD because of device limitations, pain at injection sites, inconvenience of daily injections, lack of perceived immediate benefits, insurance barriers, and costs, leading to frequent dose omissions and treatment cessation. 11,12 Thus, it has been hypothesized that LAGH products might help mitigate treatment non-adherence and potentially improve long-term treatment effects in patients with PGHD and AGHD.…”

“… 3 It is likely that reduced adherence to daily injections limits treatment outcomes as evidenced by adult height in children who required GH replacement therapy that are below the mean for the population. 4–10 …”