TY - JOUR
T1 - Severe deficiencies of IGF-I, IGF-II, IGFBP-3, ALS and paradoxically high-normal bone mass in a child with insulin-resistance syndrome (Rabson-Mendenhall type)
AU - Fowlkes, J. L.
AU - Bunn, R. C.
AU - Coleman, H. N.
AU - Hall, B.
AU - Reid, M. C.
AU - Thrailkill, K. M.
PY - 2007/10
Y1 - 2007/10
N2 - Rabson-Mendenhall syndrome is a rare genetic disorder characterized by severe insulin resistance and hyperinsulinemia due to defects in signaling through the insulin receptor. Herein, we describe a new case of Rabson-Mendenhall syndrome in which investigations of the growth hormone (GH) - insulin-like growth factor (IGF) axis - reveal severe deficiencies in total and free insulin-like growth factor-I (IGF-I), IGF-II, IGF-binding protein-3 (IGFBP-3), and the acid labile subunit (ALS). Based on these findings, we anticipated significant bone deficits, as have been described in other clinical scenarios in which the IGF axis is significantly perturbed. Long-bone studies revealed no gross malformations. Paradoxically, DXA scanning revealed a total body bone density Z-score of +2.0 (0.8 gm/cm2), suggesting an overall high-normal BMD for age and a high BMD corrected for bone or height age. The mechanisms by which BMD is protected from severe deficiencies in the IGF-axis are unknown, yet may involve enhanced IGF sensitivity, increased local production of IGFs, and/or supra-physiological concentrations of insulin substituting for the actions of IGFs in bone.
AB - Rabson-Mendenhall syndrome is a rare genetic disorder characterized by severe insulin resistance and hyperinsulinemia due to defects in signaling through the insulin receptor. Herein, we describe a new case of Rabson-Mendenhall syndrome in which investigations of the growth hormone (GH) - insulin-like growth factor (IGF) axis - reveal severe deficiencies in total and free insulin-like growth factor-I (IGF-I), IGF-II, IGF-binding protein-3 (IGFBP-3), and the acid labile subunit (ALS). Based on these findings, we anticipated significant bone deficits, as have been described in other clinical scenarios in which the IGF axis is significantly perturbed. Long-bone studies revealed no gross malformations. Paradoxically, DXA scanning revealed a total body bone density Z-score of +2.0 (0.8 gm/cm2), suggesting an overall high-normal BMD for age and a high BMD corrected for bone or height age. The mechanisms by which BMD is protected from severe deficiencies in the IGF-axis are unknown, yet may involve enhanced IGF sensitivity, increased local production of IGFs, and/or supra-physiological concentrations of insulin substituting for the actions of IGFs in bone.
KW - DXA
KW - Diabetes
KW - Donahue's Syndrome
KW - Growth
KW - Growth hormone
KW - Hyperinsulinism
KW - Insulin receptor
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U2 - 10.1016/j.ghir.2007.04.007
DO - 10.1016/j.ghir.2007.04.007
M3 - Article
C2 - 17560154
AN - SCOPUS:34548273071
SN - 1096-6374
VL - 17
SP - 399
EP - 407
JO - Growth Hormone and IGF Research
JF - Growth Hormone and IGF Research
IS - 5
ER -