Human Growth Hormone Replacement Therapy: Pharmacological and Clinical Aspects

Abstract
I. Introduction ADMINISTRATION of GH to hypopituitary children. was first reported more than 50 yr ago (1). Initially, GH was prepared from animal sources, but it became evident that nonprimate GH was inactive in man (1). Beck et al. (2) were the first to employ short-term administration of human GH (hGH) in a pituitary dwarf. This was followed by Raben's report in 1958 of an increase in linear height in a pituitary dwarf treated for 10 months with hGH (3). This finding was confirmed in a number of subsequent case reports (4–8). In 1964, Soyka et al. (9) published results from hGH therapy for up to 2.5 yr in 34 patients with short stature. The treatment schedule was 2 mg (the biopotency of the first pituitary preparations was 1 IU/mg) three times a week by the im route. The growth response was more pronounced in the hypopituitary patients, and it was concluded that treatment should be restricted to this group in view of the scarce supply of the hormone. The introduction of a radioimmunoassay (RIA) for measurements of plasma GH (10) enabled quantitative assessment of GH secretion. The diagnosis of GH deficiency was thereafter corroborated by measuring circulating GH after certain well-defined stimuli or during sleep. It was also revealed that a number of patients apparently had isolated GH deficiency (11). A review on the clinical use of GH after 1968 was presented by Frasier in 1983 (12). He summarized that therapy should be started as early as possible and administered im in a dose of 0.06–0.10 IU/kg three times a week (the biopotency of highly purified pituitary GH is 2 IU/mg). He also recommended treatment to be continuous and given until closure of the, epiphyses.