Resistance to Human Growth Hormone in Pituitary Dwarfism: Clinical and Immunologic Studies

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Abstract
Thirteen pituitary dwarfs have been treated with human growth hormone (HGH), and growth acceleration with doses of 5–7 mg/week has been observed in all but one patient. On therapy, this 7½year-old girl grew at a rate of 1.05 cm/month for 7 months. Thereafter, despite larger doses of growth hormone (15 mg/week), growth rate fell to 0.27 cm/month. This rate of growth persisted after stopping HGH. On retreatment on 2 occasions, acceleration of growth did not occur. Antibodies to HGH, absent in her serum before treatment, were repeatedly demonstrated in her serum in high concentration (HGH binding capacity up to 100 mg/l) during treatment. Comparable titers of antibody have not been found in any of the 12 other patients receiving long-term HGH treatment. The specificity of the human anti-HGH serum differed from rabbit anti-HGH serum. Whereas both monkey growth hormone (MGH) and HGH were effective inhibitors of the binding of HGH-131I by rabbit antiserum, only HGH was an effective inhibitor with human antiserum. In like manner, a crude placental extract which was an effective inhibitor for rabbit antiserum was ineffective with human anti-HGH serum.