Normal growth despite GH, IGF-I and IGF-II deficiency

A 6.5-year-old male with normal linear growth, despite septo-optic dysplasi a, panhypopituitarism and a deficient GH/IGF axis, is presented. In additio n to measuring IGF-I, IGF-II and IGFBP-3, serum IGFBP-1, -2, -4 and -5 were measured. A human osteosarcoma cell line was used to assess growth-promoti ng activity in the patient's serum. The role of leptin in linear growth in this case was investigated. There was no evidence for hyperinsulinism or hy perandrogenism. GH was undetectable upon multiple stimulation. GHBP was ele vated. Serum IGF-I (25 mu g/l), IGF-II (194 mu g/l), IGFBP-3 (0.4 mg/l), an d IGFBP-5 (87 mu g/l) levels were low compared to age-matched prepubertal c hildren. Serum IGFBP-4 level was normal. Molecular size of IGF-II in the pa tient's serum was normal, suggesting normal IGF-II bioavailability. Human o steosarcoma cell proliferation in response to the patient's serum was simil ar to sera from age-matched normal controls. Leptin levels were markedly el evated. Osteoblast cell proliferation was not stimulated by leptin. The dat a demonstrate that normal growth and osteoblast cell proliferation in this patient is not mediated by GH, total IGFs, insulin, or leptin, and suggest the presence of a yet unidentified growth factor or mechanism. The case off ers a detailed picture of binding proteins in a case of growth without GH. It introduces osteoblast cell proliferation as a method of assessing serum growth-promoting activity in such cases. It adds IGF-II and leptin to the l ist of excluded growth-promoting candidates in GH-independent growth, and f urther demonstrates our incomplete understanding of the phenomenon of growt h. (C) 1999 Harcourt Publishers Ltd.