TY - JOUR
T1 - Clinical and endocrine characteristics in atypical and classical growth hormone insensitivity syndrome
AU - Burren, C. P.
AU - Woods, K. A.
AU - Rose, S. J.
AU - Tauber, M.
AU - Price, D. A.
AU - Heinrich, U.
AU - Gilli, G.
AU - Razzaghy-Azar, M.
AU - Al-Ashwal, A.
AU - Crock, P. A.
AU - Rochiccioli, P.
AU - Yordam, N.
AU - Ranke, M. B.
AU - Chatelain, P. G.
AU - Preece, M. A.
AU - Rosenfeld, R. G.
AU - Savage, M. O.
PY - 2001
Y1 - 2001
N2 - Objective: Classical growth hormone insensitivity syndrome (GHIS) comprises a dysmorphic phenotype, extreme short stature (height SDS < 3), normal GH and low IGF-I and IGFBP-3. Wide clinical variation is recognised with classical and atypical forms. We aimed to delineate features of the milder 'atypical' GHIS phenotype, and to determine whether this correlates with milder auxological and biochemical features. Methods: Fifty-nine patients from a European series of 82 patients with GHIS, with strict diagnostic criteria of GHIS, were studied and assigned to classical or atypical GHIS groups according to facial phenotype, i.e. 'classical' required 2 of 3 recognized GHIS features (frontal bossing, mid-facial hypoplasia and depressed nasal bridge), 'atypical' required 0 or 1 of these facial features. Classical and atypical GHIS groups were compared in terms of (1) phenotypic features, including high-pitched voice, sparse hair, blue sclera, hypoglycaemia, microphallus, (2) birth length, height SDS, and (3) basal IGF-I, IGF-II, IGFBP-1, IGFBP-3, GHBP and increase in IGF-I on IGF-I generation testing. Results: Fifty patients [24 males, 26 females, aged 8.6 ± 4.6 years (mean ± SD)] had 'classical GHIS', 9 patients (7 males, 2 females, aged 7.8 ± 4.1 years) had 'atypical GHIS', 7 with normal facies. Atypical GHIS patients had lesser height deficit (Ht SDS -4.0 ± 1.4) compared to classical GHIS (-6.7 ± 1.4), less reduction in IGFBP-3 SDS (atypical -5.5 ± 3.3; classical -8.6 ± 2.4), and more had normal GHBP (> 10% binding). Other variables were also less frequent in atypical GHIS patients: high-pitched voice 11% (70% classical), sparse hair 11% (42% classical), blue sclera 0% (38% classical), hypoglycaemia 11% (42% classical), and microphallus 14% (1 of 7 males), compared to 79% of classical (19 of 24 males). Conclusions: Atypical GHIS patients, with relatively normal facial appearance, demonstrate less height defect and biochemical abnormalities compared to classical patients. GH insensitivity may be present in children with short stature and an otherwise normal appearance.
AB - Objective: Classical growth hormone insensitivity syndrome (GHIS) comprises a dysmorphic phenotype, extreme short stature (height SDS < 3), normal GH and low IGF-I and IGFBP-3. Wide clinical variation is recognised with classical and atypical forms. We aimed to delineate features of the milder 'atypical' GHIS phenotype, and to determine whether this correlates with milder auxological and biochemical features. Methods: Fifty-nine patients from a European series of 82 patients with GHIS, with strict diagnostic criteria of GHIS, were studied and assigned to classical or atypical GHIS groups according to facial phenotype, i.e. 'classical' required 2 of 3 recognized GHIS features (frontal bossing, mid-facial hypoplasia and depressed nasal bridge), 'atypical' required 0 or 1 of these facial features. Classical and atypical GHIS groups were compared in terms of (1) phenotypic features, including high-pitched voice, sparse hair, blue sclera, hypoglycaemia, microphallus, (2) birth length, height SDS, and (3) basal IGF-I, IGF-II, IGFBP-1, IGFBP-3, GHBP and increase in IGF-I on IGF-I generation testing. Results: Fifty patients [24 males, 26 females, aged 8.6 ± 4.6 years (mean ± SD)] had 'classical GHIS', 9 patients (7 males, 2 females, aged 7.8 ± 4.1 years) had 'atypical GHIS', 7 with normal facies. Atypical GHIS patients had lesser height deficit (Ht SDS -4.0 ± 1.4) compared to classical GHIS (-6.7 ± 1.4), less reduction in IGFBP-3 SDS (atypical -5.5 ± 3.3; classical -8.6 ± 2.4), and more had normal GHBP (> 10% binding). Other variables were also less frequent in atypical GHIS patients: high-pitched voice 11% (70% classical), sparse hair 11% (42% classical), blue sclera 0% (38% classical), hypoglycaemia 11% (42% classical), and microphallus 14% (1 of 7 males), compared to 79% of classical (19 of 24 males). Conclusions: Atypical GHIS patients, with relatively normal facial appearance, demonstrate less height defect and biochemical abnormalities compared to classical patients. GH insensitivity may be present in children with short stature and an otherwise normal appearance.
KW - GHBP
KW - Growth hormone insensitivity syndrome
KW - Growth hormone receptor
KW - IGF-I
KW - IGFBP-3
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U2 - 10.1159/000049983
DO - 10.1159/000049983
M3 - Article
C2 - 11549873
AN - SCOPUS:17944365054
SN - 0301-0163
VL - 55
SP - 125
EP - 130
JO - Hormone Research
JF - Hormone Research
IS - 3
ER -