Final Height Following Growth HormoneTreatment of Idiopathic Growth Hormone

Deficiency in KIGS

Wayne S Cutfield, Anders Lindberg, Pierre Chatelain, David A Price, Kerstin Albertsson-Wikland, Patrick Wilton, and Michael B Ranke

on behalf of the KIGS International Board

KIGS 10 Year Book, 1999

W Cutfield - KIGS 10 Year Book, 1999

Variable Male patients Female patients

Total (n)– Caucasian (n)– Japanese (n)

223154 69

146115 31

Chronological age (years) 10.4 (5.1-13.4) 8.5* (4.1-12.1)

Birth weight (SDS) -0.6 (-1.8 to 0.8) -0.5 (-2.5 to 1.2)

MPH (SDS)– Caucasian (n)– Japanese (n)

-0.9 -2.1

(-2.6 to 0.9)(-3.4 to -0.9)

-0.7 -1.9

(-2.5 to 0.9)(-3.3 to -0.9)

Max GH peak (µg/L) 3.2 (0.7-8.4) 3.4 (0.6-8.0)

Height (SDS)– Caucasians– Japanese

-2.8 3.1

(-4.5 to -1.8)(-4.8 to -2.2)

-3.4* -3.3

(-5.0 to -2.1)(-4.4 to -2.8)

Multiple pituitary hormonedeficiencies (%)

52 46

Induced puberty (%) 33 27

Baseline characteristics of patients with idiopathic GHD prior to commencement of GH therapya

MPH, mid-parental height; SDS, standard deviation score* p<0.01aValues expressed as medians (10th - 90th percentiles)

W Cutfield - KIGS 10 Year Book, 1999

GH treatment regimens and auxological characteristics of patients with idiopathic GHD who have achieved final heighta

Variable Male patients Female patients

Duration of GH treatment(years)

8.3 (5.6-13.5) 8.0 (5.3-13.2)

GH dose (IU/kg/week) 0.48 (0.32-0.71) 0.53* (0.35-0.75)

GH injections per week 5.3 (3.2-6.9) 5.1 (3.0-6.9)

Chronological age (years) 18.9 (17.5-21.7) 17.1* (15.4-20.1)

Height (SDS)– Caucasians– Japanese

-0.9-2.2

(-2.6 to 0.6)(-3.5 to -1.2)

-1.2 -2.6*

(-2.8 to 0.4)(-4.3 to -2.0)

Final height – initial height(SDS)

1.8 (0.4-3.3) 1.6 (0.3-4.1)

Final height – MPH (SDS) -0.3 (-2.0 to 1.0) 0.7* (-2.7 to 0.5)

MPH, mid-parental height; SDS, standard deviation score* p<0.01aValues expressed as medians (10th - 90th percentiles)

W Cutfield - KIGS 10 Year Book, 1999

Final height achieved by male subjects with idiopathic growth hormone deficiency

(1/2)

130

135

140

145

150

155

160

165

170

175

180

185

190

195

10 12 14 16 18 20 22 24 26 28 30

Chronological age

Hei

ght (

cm)

Means ( ), +2 SD ( ),and -4 SD ( ).

Final height achieved by female subjects with idiopathic growthhormone deficiency

W Cutfield - KIGS 10 Year Book, 1999

(2/2)

110

115

120

125

130

135

140

145

150

155

160

165

170

175

180

185

Chronological age

10 12 14 16 18 20 22 24 26 28 30

Hei

ght (

cm)

Means ( ), +2 SD ( ),and -4 SD ( ).

W Cutfield - KIGS 10 Year Book, 1999

Comparison of patients with spontaneous onset of puberty andthose with induced puberty for whom auxological data were

available at onset of puberty (medians)Variable Male patients Female patients

Spontaneouspuberty(n=52)

Inducedpuberty(n=52)

Spontaneouspuberty(n=62)

Inducedpuberty(n=16)

At start of GH treatmentChronological age (years) 9.6 9.5 8.5 7.5Max GH peak (µg/L) 4.1 1.7* 4.2 1.6*MPH (SDS) -0.04 -0.6 -0.6 -0.3Height (SDS) -2.7 -3.1 -3.1 -3.5Height – MPH (SDS) -2.8 -2.6 -2.7 -3.3

At start of pubertyChronological age (years) 13.8 15.5* 12.9 14.2*Duration of GH therapy (years) 3.4 6.3* 3.8 6.4*Height (SDS) -1.7 -1.4 -1.7 -1.1Pubertal height – initial height(SDS)

1.1 1.7 1.5 2.0

Height – MPH (SDS) -1.2 -0.8 -0.9 -0.4

At final heightChronological age (years) 18.4 19.3 16.9 17.9Duration of puberty (years) 4.3 3.7 3.8 3.1Total pubertal growth (cm) 25.3 17.1 15.3 11.8Height (SDS) -0.9 -1.0 -1.8 -0.9Final height – pubertal height(SDS)

0.5 0.4 -0.2 0.1

Final height – initial height (SDS) 1.9 2.2 1.6 2.4Final height – MPH (SDS) -0.6 -0.2 -0.8 -0.2

MPH, mid-parental height; SDS, standard deviation score, * p<0.01

Variable rValue pValue

MPH (SDS) 0.62 <0.001

Total GH dose (IU) 0.49 <0.001

Height at start of GH (SDS) 0.45 <0.001

Injections (n/week) 0.37 <0.001

Birth weight (SDS) 0.31 <0.001

Weight at start of GH (SDS) 0.32 <0.001

Duration of GH treatment(years)

0.28 <0.001

Max GH peak (µg/L) -0.25 <0.001

Height velocity at 1 year (SDS) 0.20 <0.004

Chronological age (years) -0.19 <0.001

Mean GH dose (IU/kg/week) 0.15 NS

MPH, mid-parental height ; NS, not significant

W Cutfield - KIGS 10 Year Book, 1999

Relation of pretreatment and treatment variables to final height based on simple linear correlations

Patients(n)

Final height(SDS)

MPH(SDS)

Final height – MPH(SDS)

NCGS 1997– male– female

7249

-0.7-0.7

-0.3-0.2

-0.6-0.4

KIGS– male– female

223146

-1.4-2.0

-0.9-1.4

-0.3-0.7

Influence of mid-parental height on final height in the National Cooperative Growth Study (NCGS)a

and in KIGS subjects

W Cutfield - KIGS 10 Year Book, 1999

aNCGS data from Blethen et al (1997)

Difference in height SDS between idiopathic GH-deficient male subjects with induced or with spontaneous puberty at start of GH treatment, onset of puberty and final height

W Cutfield - KIGS 10 Year Book, 1999

Spontaneous InducedGH start

Spontaneous InducedPubertal onset

Spontaneous InducedFinal height

Hei

ght (

SDS)

Data are shown as 25th and 75 percentiles (box plots),medians (rules) and means (dots), with whiskers at the 10th and 90th percentiles

Difference in height SDS between idiopathic GH-deficient female subjects with induced or with spontaneous puberty at start of GH treatment, onset of puberty and final height

W Cutfield - KIGS 10 Year Book, 1999

Spontaneous InducedGH start

Spontaneous InducedPubertal onset

Spontaneous InducedFinal height

Hei

ght (

SDS)

Data are shown as 25th and 75 percentiles (box plots),medians (rules) and means (dots), with whiskers at the 10th and 90th percentiles