Role of the GH-IGF Axis in Statural Growth and Harmonious Body Proportionality: In Search of Vitruvian Man?

CONTEXT: Body proportions are the objective parameters of harmonious growth and reflect the interplay of genetic, environmental, metabolic, and hormonal actions. Mutations in the growth hormone receptor gene (GHR) result in severe growth failure. The study of individuals affected with these mutations can inform us about the role of growth peptides in harmonious, proportional growth. OBJECTIVE: The aim of this study was to critically assess the role of the growth hormone-insulin-like growth factor (GH-IGF) axis in statural growth and in particular body proportionality. METHODS: In this epidemiological, noninterventional study, we compared the anthropometric measurements and body proportions of an Ecuadorian cohort of adults with GH insensitivity (GHI) due to a homozygous mutation at codon 180/exon 6 of GHR, to their carrier and noncarrier relatives, and to noncarrier unrelated controls. We also investigated the relations between serum IGF-I concentrations and auxological determinations. RESULTS: In this cohort of 201 adults, sex-specific distributions of height (Ht), lower segment, upper segment, arm span, head circumference (HC), and hand and foot length were lower in the GHI individuals than in the other groups. The GHI individuals had the lowest lower segment/Ht, the highest upper segment/Ht, the lowest arm span/Ht and the highest HC/Ht ratio. Hand and foot length/Ht ratios were not uniformly affected. Serum IGF-I concentrations displayed a positive logarithmic correlation with all body measurements but were negatively correlated with the HC/Ht ratio. CONCLUSION: These findings indicate that individuals homozygous for the GHR mutation have disharmonious body proportions due to abnormal GH/IGF-I action on the growth of the long bones. Contrary to common assumptions, disruption of the GH-IGF axis results in disproportionality and disharmonious growth.