Laron-type dwarfism with apparently normal high affinity serum growth hormone-binding protein

Abstract

Objective: Normal serum contains a high affinity GH-binding protein, which appears to be identical with the extracellular domain of the GH receptor. It is normally absent from the serum of patients with Laron-type dwarfism. We wished in this study to define the serum GH-binding protein status of a family with Laron-type dwarfism.

Design and patients: We performed an open case study of an Asian family in which three sisters (aged 3 to 15 years) had the phenotype of Laron-type dwarfism. Sera from a fourth, unrelated girl with Laron-type dwarfism and subjects without endocrine disorders were used as control samples.

Measurements: Laron-type dwarfism was confirmed by demonstration of elevated serum GH levels and low serum IGF-I levels on immunoassay, with serum IGF-I levels failing to rise during treatment with GH. Serum GH-binding proteins were characterized using gel chromatography on Sephacryl S-100HR following incubation of serum with 125I-GH, Scatchard analysis of ligand binding, and by polyacrylamide gel electrophoresis after covalent cross-linking to 125I-GH.

Results: All members of the family had high affinity serum GH-binding protein activity similar in size, circulating levels and apparent affinity for GH to that of normal subjects. This contrasted with the very low serum GH-binding protein activity in the unrelated child with Laron-type dwarfism and previous reports of serum GH-binding protein levels in this disorder.

Conclusions: The affected patients may possess a novel biochemical defect which results in GH-resistance and reduced production of IGF-I in the presence of normal serum GH-binding protein levels.