J Clin Endocrinol Metab. 2024 Nov 28:dgae835. doi: 10.1210/clinem/dgae835. Online ahead of print.
ABSTRACT
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.
METHODS: In this epidemiological, non-interventional study, we compared the anthropometric measurements and body proportions of an Ecuadorian cohort of adult subjects with GH insensitivity (GHI) due to a homozygous mutation at codon 180/exon 6 of the GHR, to their carrier and non-carrier relatives, and to non-carrier unrelated controls. We also investigated the relations between serum IGF-I concentrations and auxological determinations.
RESULTS: In this cohort of 201 adults, gender-specific distributions of height (Ht), lower segment, upper segment, arm span, head circumference (HC), hand and foot length were lower in the GHI subjects 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 head circumference/Ht ratio. Hand and foot length/Ht ratios were not uniformly affected. Serum IGF-I concentration displayed a positive logarithmic correlation with all body measurements but were negatively correlated with the head circumference/Ht ratio.
CONCLUSIONS: These findings indicate that subjects 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.
PMID:39607890 | DOI:10.1210/clinem/dgae835
