Administration of Growth Hormone to Patients with Familial Dwarfism with High Plasma Immunoreactive Growth Hormone: Measurement of Sulfation Factor, Metabolic and Linear Growth Responses

Familial dwarfism with high plasma IR-HGH is a syndrome which is clinically indistinguishable from hereditary monotropic dwarfism due to lack of growth hormone (HGH) secretion. Furthermore, in both types of dwarfism there is a spontaneous hypoglycemia, hypoglycemia nonresponsiveness after the injection of insulin, and a reduced insulin response after arginine infusion. The metabolic and linear growth response to exogenous HGH was studied in 16 patients with this syndrome and compared to that in 19 patients with pituitary dwarfism due to HGH deficiency (isolated or concomitant with other hormones), as well as in 4 newborns and a patient with active acromegaly who had elevated concentrations of HGH in the plasma. A number of important differences in response were observed. After intravenous HGH administration, patients with familial dwarfism and high HGH had a smaller rise in plasma FFA than occurred in true pituitary dwarfs. Administration of HGH intramuscularly for 4 days induced no rise in plasma SF, less decrease in urinary nitrogen, and less prominent calciuria in familial dwarfs with high IR-HGH as compared to true pituitary dwarfs. Treatment of the familial dwarfs with high plasma IR-HGH with exogenous HGH for periods of 5–17 months failed to stimulate significant growth in most cases. As yet, we do not know just what is the basic defect in familial dwarfism with high plasma IR-HGH. The primary lack of a sulfation factor cannot readily explain the manifold metabolic changes found, with the exception of dwarfism. It is suggested that at least part of their resistance to exogenous HGH is due to saturation of peripheral tissue receptors of HGH by an abnormal GH. This hypothesis of competitive saturation is supported by the findings that newborns and a patient with acromegaly were resistant to the influence of exogenous HGH while the concentration of plasma HGH was high, but showed a normal response when HGH levels decreased.