Regulation of growth and plasma growth hormone in a Laron's dwarf

Abstract

Laron identified a group of children with severe growth failure and high levels of immunoreactive human growth hormone (IR-HGH). To investigate why these patients often have elevated HGH, we studied a 7½ year old Saudia Arabian boy with a height of 85 cm (HA 2yrs) and basal IR-HGH levels of 32 to 84 ng/ml (normal—less than 5 nanagrams per ml). Fasting blood sugars were often in the hypoglycemic range, and hyperglycemia induced by glucose infusion did not suppress his high IR-HGH. The serum IR-HGH was increased markedly by arginine infusion. High dose HGH treatment (7.5 mg q 12 hrs × 9 doses) did not modify his IR-HGH response 1 hour after arginine (increment over control was 111 and 121 ng/ml before and after treatment). Plasma sulfation factor (SF) was low and did not rise with treatment, as it does in the usual HGH deficient patient. Chronic adminsitration of HGH (2.5 mg × per week) produced a modest growth acceleration of 2.6 cm over the 5 months period compared to an expected response of 6.5 to 12 cm per year, in patients lacking HGH. These studies suggest that the persistently elevated IR-HGH is due to either a lack of SF to suppress the hypothalamic growth hormone releasing factor or that the hypothalamic HGH receptors share the same defects as those receptors responsible for the initiation of SF synthesis. Regardless of the interpretation, the IR-HGH in these patients does not appear to be under the hypothalamic control system demonstrable in normal individuals.