Clinical features and endocrine status in patients with growth hormone insensitivity (Laron syndrome).
Twenty-seven patients with GH insensitivity were identified from 44 possible cases, using a scoring system based on height standard deviation score (SDS), basal GH, insulin-like growth factor-I (IGF-I), IGF-I response to IGF-I generation test, and GH-binding protein (GH-BP) determinations. The 27 cases were from 8 European countries and Australia. Clinical features were as follows: age 2.8-22.6 yr; 12 male, 15 female, 19 prepubertal. Birth weight was median -0.72 SDS (1.75(-)-3.29) and birth length, median -1.59 SDS (0.63(-)-3.63). Hypoglycemia had been documented in 33% of the cases, and micropenis was present in 58% of the males. At assessment, height was median -6.1 SDS (-3.8(-)-10.2), weight was median -3.2 SDS (-0.1 to -5.2), and percentage weight for height, median 111.3 (72-271). Puberty was absent in 2 boys aged 15 yr and in 3 girls aged 13 yr. Bone age was delayed in 19 of the 27 patients. Endocrine investigations showed basal serum GH median 17 micrograms/L (0.5-79), IGF-I values less than 5th percentile, and all except 2, age less than 8 yr, less than 0.1 percentile for age. Percentage increment of IGF-I during IGF-I generation test (hGH 0.1 U/kg body weight daily x 4) did not exceed twice the intraassay coefficient of variation, being less than 0.1 percentile for age. IGF-II was median 135.0 micrograms/L (62-232), all values being less than 5th percentile for age. Insulin-like growth factor binding protein-3 (IGFBP-3) values were median 0.53 mg/L (0.10-1.17 mg/L), all being less than 5th percentile for age. IGFBP-3 values after hGH remained less than 5th percentile. IGFBP-1 values showed the normal fall with age, some being above the normal range; IGFBP-2 values were normal. There was a positive correlation between height SDS and IGF-II SDS (r = 0.66, P < 0.001) and IGFBP-3 (r = 0.64, P < 0.001). Specific binding of [125I]hGH to GH-BP was undetectable in 18 patients and extremely low (< or = 5.6%) in 2. GH-BP was normal (14.2-45.9% radioactivity) in 7 subjects, all female, demonstrating that normal GH-BP does not exclude GH insensitivity.
Savage
M O
MO
Department of Endocrinology, St. Bartholomew's Hospital, London, United Kingdom.
Blum
W F
WF
Ranke
M B
MB
Postel-Vinay
M C
MC
Cotterill
A M
AM
Hall
K
K
Chatelain
P G
PG
Preece
M A
MA
Rosenfeld
R G
RG
D000293:Adolescent; D000328:Adult; D000365:Age Determination by Skeleton; D002352:Carrier Proteins / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D006128:Growth; D006130:Growth Disorders / Q000097:blood* / Q000503:physiopathology; D013006:Growth Hormone / Q000097:blood / Q000502:physiology*; D006728:Hormones / Q000097:blood*; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007335:Insulin-Like Growth Factor II / Q000032:analysis; D008297:Male; D011627:Puberty; D013577:Syndrome
D002352:Carrier Proteins; D006728:Hormones; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D013006:Growth Hormone; C051815:somatotropin-binding protein