Laron's dwarfism: Studies on the nature of the defect

Abstract

Laron's syndrome is characterized by severe dwarfism, high circulating levels of immunoreactive growth hormone, and a failure to generate somatomedin in response to administration of human growth hormone. Studies conducted in a 7 1/2-year-old boy with the syndrome indicate that the hypothalamic-pituitary mechanisms controlling growth hormone secretion are intact. However, those controlling the suppression of growth hormone release seem to be inoperative. The administration of exogenous human growth hormone failed to produce an acute metabolic response as measured by mineral retention, nitrogen retention, somatomedin generation, or release of free fatty acid from adipose tissue; however, an unsustained growth response to long-term administration of human growth hormone was observed. The circulating growth hormone resembled normal human growth hormone immunologically and has the usual prolactin-like activity. These data suggest that the primary defect is tissue unresponsiveness to normal human growth hormone. An abnormality in the structure of growth hormone which is not essential for prolactin activity and immunoreactivity and a slow rate of growth hormone degradation in these patients cannot be excluded by available data.