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Low-dose growth hormone-releasing hormone tests: a dose–response study

Spoudeas HA, Winrow AP, Hindmarsh PC, Brook CGD. Low-dose growth hormone-releasing hormone tests: a dose-response study. Eur J Endocrinol 1994;131:238–45. ISSN 0804–4643

We have evaluated parameters of the serum growth hormone (GH) concentration response to saline and 1-, 10- and 100-µg intravenous bolus doses of amide analogue of GH-releasing hormone (GHRH (1–29)NH₂) given in random order to 10 adult male volunteers of median body weight 68 (60–90)kg. Compared with saline, both 10- and 100-µg GHRH(1–29)NH₂ doses (but not 1 µg) resulted in significant peak GH responses (means and 95% confidence intervals: 24.03 (11.22–51.29) vs 26.09 (16.40–41.50) mU/l, respectively). Although the average rate of serum GH rise was similar after both 10 µg (2.05 (1.13–2.97) mU · l^–1 · min^–1) and 100 µg of GHRH(1–29)NH₂ (1.52 (0.69–2.35) mU·1^–1 · min^–1; ANOVA F = 0.93, p = 0.35), the average rate of serum GH decline after peak GH was slower after the higher dose (10 µg vs 100 µg: 0.65 (0.40–0.90) vs 0.37 (0.23–0.50) mU·1^–1·min^–1; ANOVA F = 5.14, p = 0.04), suggesting continued GH secretion. Increasing GHRH(1–29)NH₂ doses delayed the time to peak GH (1 µg: 7.00 (3.50–10.52) min; 10 µg: 15.80 (13.62–17.98) min; 100 µg: 24.80 (18.40–31.12) min) and serum GH levels were still elevated significantly 2 h after injection of 100 µg GHRH(1–29)NH₂ compared with other doses (saline: 0.98 (0.48–2.04) mU/1; 1 µg: 0.68 (0.48–0.93) mU/1; 10 µg: 1.07 (0.56–2.04) mU/1; 100 µg: 5.01 (2.34–10.86) mU/l; ANOVA F = 11.10, p < 0.001). In a second study we tested five adult male volunteers with lower doses (0.5–10 µg) of GHRH(1–29)NH₂. Consistent responses were observed only at doses equal to or greater than 2.5 µg and all occurred between 10 and 25 min. The estimated ed50 for GHRH(1–29)NH₂ from the combined study data was 7.5 µg (0.08 µg/kg; range 0.06–0.12 µg/kg). The 10-µg dose of GHRH(1–29)NH₂ was a maximal stimulus in all release parameters examined and GH peaks of < 15 mU/l (10th centile) should be considered potentially abnormal. Lower doses of GHRH(1–29)NH₂ released GH quicker than higher doses, which simply prolonged the response, possibly by causing release from different pools. Our results suggest that sampling at 0, 10, 15, 20 and 25 min after a 10-µg dose of GHRH(1–29)NH₂ will identify all GH peaks.

CGD Brook, The Endocrine Unit, Middlesex Hospital, Mortimer Street, London WIN 8AA, UK

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