Clinical and endocrine characteristics in atypical and classical growth hormone insensitivity syndrome

Objective: Classical growth hormone insensitivity syndrome (GHIS) comprises a dysmorphic phenotype, extreme short stature (height SIDS < 3), normal GH and low IGF-I and IGFBP-3. Wide clinical variation is recognised with clas sical and atypical forms. We aimed to delineate features of the milder 'aty pical' 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 o f GHIS, were studied and assigned to classical or atypical GHIS groups acco rding to facial phenotype, i.e. 'classical' required 2 of 3 recognized GHIS features (frontal bossing, mid-facial hypoplasia and depressed nasal bridg e), 'atypical' required 0 or 1 of these facial features. Classical and atyp ical GHIS groups were compared in terms of (1) phenotypic features, includi ng high-pitched voice, sparse hair, blue sclera, hypoglycaemia, microphallu s, (2) birth length, height SIDS, and (3) basal IGF-I, IGF-II, IGFBP-1, IGF BP-3, GHBP and increase in IGF-I on IGF-I generation testing. Results: Fift y patients [24 males, 26 females, aged 8.6 +/- 4.6 years (mean SD)] had 'cl assical 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 he ight deficit (Ht SIDS -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% class ical), sparse hair 11% (42% classical), blue sclera 0% (38% classical), hyp oglycaemia 11% (42% classical), and microphallus 14% (1 of 7 males), compar ed to 79% of classical (19 of 24 males). Conclusions: Atypical GHIS patient s, with relatively normal facial appearance, demonstrate less height defect and biochemical abnormalities compared to classical patients. GH insensiti vity may be present in children with short stature and an otherwise normal appearance. Copyright (C) 2001 S. Karger AG, Basel.