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Dose-Response Studies With Biosynthetic Human Growth Hormone (GH) in GH-Deficient Patients

Institute of Experimental Clinical Research, Second University Clinic of Internal Medicine Kommunehospital, Aarhus, Denmark
The Department of Clinical Biochemistry, Royal Victoria Infirmary Newcastle-upon-Tyne, England

Address requests for reprints to: Dr. Jens Jorgensen, Second University Clinic of Internal Medicine, Kommunehospitalet, DK-8000 Aarhus, Denmark.

Increasing doses of biosynthetic human GH (RhGH) were given sc to seven GH-deficient patients for three consecutive 14-day periods (2, 4, and 6 IU/day at 2000 h), followed by 14 days of no GH therapy. At the end of each period each patient was hospitalized for frequent blood sampling from 2000 to 1100 h the following day. A dose-dependent increase in serum GH and serum insulin-like growth factor I (IGF-I) levels occurred. However, the time course of the serum IGF-I concentrations was different on the four occasions; there was a significant fall in the evening when no therapy was given (P < 0.01), a significant increase after injections of 2 IU R-hGH, and constant levels during treatment with 4 and 6 IU R-hGH. Plasma glucose levels were within the normal range, with a significantly lower fasting level (at 0400 h) when no GH was given. Breakfast induced a plasma glucose rise when GH was administered, but no rise without GH, and a postprandial serum insulin response that was GH dose dependent. GH therapy increased serum FFA (P < 0.05) and blood 3-hydroxybutyrate levels, but had no effect on blood alanine or lactate or serum triglyceride and cholesterol levels.

We conclude that the serum IGF-I response to GH is dose dependent, and that a GH replacement dose of 2 IU/day (equalling 1.5 IU/m²-day) is insufficient to maintain normal diurnal serum IGF-I levels. Furthermore, a GH-independent diurnal variation in serum IGF-I in these patients is suggested. This GH preparation also has diabetogenic and lipolytic actions.

Received November 23, 1987.

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