[Recent progress in the diagnosis of growth hormone (GH) disorders]

Growth hormone (GH) disorders are characterized with clinical presentation of GH excess or deficiency. The pathogenesis and pathophysiology of GH disorders have been extensively studied with the sake of recent development of sensitive immunoassays and molecular cell biology. Highly sensitive immunoassays for GH have revealed the normal and abnormal GH secretory dynamics even under the detectable levels by conventional radioimmunoassay. Glucose loading clearly suppressed GH levels less than 1ng/ml in normal subjects. Clinical utility of insulin like growth factor-I (IGF-I) for diagnosing GH disorders was also evaluated. We have established the age- and sex-matched reference values of IGF-I and IGF binding protein-3 (IGFBP-3) in Japanese. Both IGF-I and IGFBP-3 had the similar diagnostic values for GH deficiency. Genetic alterations in GH secreting pituitary adenomas have been extensively studied. Gs alpha mutation has been found in about 30-40% of acromegaly. The prevalence of this mutation was previously considered low but recent studies showed even higher incidence in Japan. Other oncogenic mutations were considered rare in acromegaly. It is noteworthy that GH secreting adenoma tissues had high content of activated cyclic AMP responsive element-binding proteins (CREB). We have identified new mutation in GH-1 gene in patients with familial isolated GH deficiency type II, which resulted in the skipping of exon 3.