title: Evaluation of growth hormone axis and responsiveness to growth stimulation of short children with osteogenesis imperfecta.
abstract: Growth deficiency is a cardinal manifestation of severe Osteogenesis Imperfecta (OI) and occurs frequently in moderate to mild OI. We have investigated the status of the hormones related to growth in 28 children with OI. Our goals were to determine whether there were any abnormalities of these hormones, whether the abnormalities correlated with types of OI, and whether OI bone could be safely stimulated to grow. The study group included 14 females and 14 males. Using the criteria developed by Sillence et al. [1979], 13 children had OI type III, 12 had OI type IV, and 3 had OI type I. Evaluation included 3 standard hGH provocative tests (AITT, L-Dopa), GRF stimulation, 24 hr q20 minute sampling of unstimulated growth hormone, and a somatomedin generation test. All patients except one had normal responses to standard provocative stimuli. Responses to GRF fell into 2 groups: one with a mean response similar to that of normal children, and one with a mean response resembling that of GH deficient children. The group with low response to GRF had a significantly lower area under the curve in the 24-hr test of unstimulated GH than did the normal response group. The OI children as a group showed a blunted IGF-1 response during the Somatomedin Generation Test, with 18/28 children having less than a two-fold stimulation. No test results correlated with OI type. Ten OI children were enrolled in a pilot growth stimulation study. Two children received protropin and 8 received clonidine for at least 6 months. Both children treated with protropin and 4/8 treated with clonidine experienced at least a doubling of their pre-treatment growth rates. Lack of growth hormone response did not correlate with type of OI or parameters from the hormonal evaluation. We speculate that there is a group of OI children who have a hypoactive growth hormone axis. Some OI bone appears to respond to GH and a treatment trial with protropin is planned for a larger number of children.
authors.affiliation: Human Genetics Branch, NICHD, NIH, Bethesda, Maryland 20892.
authors.forename: J C
authors.initials: JC
authors.lastname: Marini
authors.forename: S
authors.initials: S
authors.lastname: Bordenick
authors.forename: G
authors.initials: G
authors.lastname: Heavner
authors.forename: S
authors.initials: S
authors.lastname: Rose
authors.forename: G P
authors.initials: GP
authors.lastname: Chrousos
mesh_terms: D001827:Body Height; D005260:Female; D006130:Growth Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013007:Growth Hormone-Releasing Hormone / Q000627:therapeutic use; D006801:Humans; D008297:Male; D010013:Osteogenesis Imperfecta / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D010865:Pilot Projects; D010908:Pituitary Hormones, Anterior / Q000378:metabolism*
chemical_list: D010908:Pituitary Hormones, Anterior; D013007:Growth Hormone-Releasing Hormone